Search results for: generation z

Authors: M. Gomaa Abdoelatef, Robert M. Field, Lee, Yong-Kwan

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Growing human populations have placed increased demands on water supplies and a heightened interest in desalination infrastructure. Key elements of the economics of desalination projects are thermal and electrical inputs. With growing concerns over the use of fossil fuels to (indirectly) supply these inputs, coupling of desalination with nuclear power production represents a significant opportunity. Individually, nuclear and desalination technologies have a long history and are relatively mature. For desalination, Reverse Osmosis (RO) has the lowest energy inputs. However, the economically driven output quality of the water produced using RO, which uses only electrical inputs, is lower than the output water quality from thermal desalination plants. Therefore, modern desalination projects consider that RO should be coupled with thermal desalination technologies (MSF, MED, or MED-TVC) with attendant steam inputs to permit blending to produce various qualities of water. A large nuclear facility is well positioned to dispatch large quantities of both electrical and thermal power. This paper considers the supply of thermal energy to a large desalination facility to examine heat balance impact on the nuclear steam cycle. The APR1400 nuclear plant is selected as prototypical from both a capacity and turbine cycle heat balance perspective to examine steam supply and the impact on electrical output. Extraction points and quantities of steam are considered parametrically along with various types of thermal desalination technologies to form the basis for further evaluations of economically optimal approaches to the interface of nuclear power production with desalination projects. In our study, the thermodynamic evaluation will be executed by DE-TOP which is the IAEA desalination program, it is approved to be capable of analyzing power generation systems coupled to desalination systems through various steam extraction positions, taking into consideration the isolation loop between the APR-1400 and the thermal desalination plant for safety concern.

Keywords: APR-1400, desalination, DE-TOP, IAEA, MSF, MED, MED-TVC, RO

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Authors: Jie Xu, Zengshan Tian, Ze Li

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Previous indoor ranging or localization systems achieving high accuracy time of flight (ToF) estimation relied on two key points. One is to do strict time and frequency synchronization between the transmitter and receiver to eliminate equipment asynchronous errors such as carrier frequency offset (CFO), but this is difficult to achieve in a practical communication system. The other one is to extend the total bandwidth of the communication because the accuracy of ToF estimation is proportional to the bandwidth, and the larger the total bandwidth, the higher the accuracy of ToF estimation obtained. For example, ultra-wideband (UWB) technology is implemented based on this theory, but high precision ToF estimation is difficult to achieve in common WiFi or Bluetooth systems with lower bandwidth compared to UWB. Therefore, it is meaningful to study how to achieve high-precision ranging with lower bandwidth when the transmitter and receiver are asynchronous. To tackle the above problems, we propose a two-way channel error elimination theory and a frequency hopping-based carrier phase ranging algorithm to achieve high accuracy ranging under asynchronous conditions. The two-way channel error elimination theory uses the symmetry property of the two-way channel to solve the asynchronous phase error caused by the asynchronous transmitter and receiver, and we also study the effect of the two-way channel generation time difference on the phase according to the characteristics of different hardware devices. The frequency hopping-based carrier phase ranging algorithm uses frequency hopping to extend the equivalent bandwidth and incorporates a carrier phase ranging algorithm with multipath resolution to achieve a ranging accuracy comparable to that of UWB at 400 MHz bandwidth in the typical 80 MHz bandwidth of commercial WiFi. Finally, to verify the validity of the algorithm, we implement this theory using a software radio platform, and the actual experimental results show that the method proposed in this paper has a median ranging error of 5.4 cm in the 5 m range, 7 cm in the 10 m range, and 10.8 cm in the 20 m range for a total bandwidth of 80 MHz.

Keywords: frequency hopping, phase error elimination, carrier phase, ranging

Procedia PDF Downloads 122

Authors: L. Shafiq, A. Rigby

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All polyethylene processes are highly exothermic, and the safe removal of the heat of reaction is a fundamental issue in the process design. In slurry and gas processes, the velocity of the polymer particles in the reactor and external coolers can be very high, and under certain conditions, this can lead to static charging of these particles. Such static charged polymer particles may start building up on the reactor wall, limiting heat transfer, and ultimately leading to severe reactor fouling and forced reactor shut down. Statsafe™ is an FDA approved anti-fouling additive currently used around the world for polyolefin production as an anti-fouling additive. The unique polymer chemistry aids static discharge, which prevents the build-up of charged polyolefin particles, which could lead to fouling. Statsafe™ is being used and trailed in gas, slurry, and a combination of these technologies around the world. We will share data to demonstrate how the use of Statsafe™ allows more stable operation at higher solids level by eliminating static, which would otherwise prevent closer packing of particles in the hydrocarbon slurry. Because static charge generation depends also on the concentration of polymer particles in the slurry, the maximum slurry concentration can be higher when using Statsafe™, leading to higher production rates. The elimination of fouling also leads to less downtime. Special focus will be made on the impact anti-static additives have on catalyst performance within the polymerization process and how this has been measured. Lab-scale studies have investigated the effect on the activity of Ziegler Natta catalysts when anti-static additives are used at various concentrations in gas and slurry, polyethylene and polypropylene processes. An in-depth gas phase study investigated the effect of additives on the final polyethylene properties such as particle size, morphology, fines, bulk density, melt flow index, gradient density, and melting point.

Keywords: anti-static additives, catalyst performance, FDA approved anti-fouling additive, polymerisation

Procedia PDF Downloads 203

Authors: M. P. Dandekar, A. P. Bharne, P. T. Borkar, D. M. Kokare, N. K. Subhedar

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Ethanol ingestion by the mother ensue adverse consequences for her offspring. Herein, we examine the behavioral phenotype and neural substrate of the offspring of the mother on ethanol. Female rats were fed with ethanol-containing liquid diet from 8 days prior of conception and continued till 25 days post-parturition to coincide with weaning. Behavioral changes associated with anxiety, depression and learning and memory were assessed in the offspring, after they attained adulthood (day 85), using elevated plus maze (EPM), forced swim (FST) and novel object recognition tests (NORT), respectively. The offspring of the alcoholic mother, compared to those of the pair-fed mother, spent significantly more time in closed arms of EPM and showed more immobility time in FST. Offspring at the age of 25 and 85 days failed to discriminate between novel versus familiar object in NORT, thus reflecting anxiogenic, depressive and amnesic phenotypes. Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CART) is known to be involved in central effects of ethanol and hence selected for the current study. Twenty-five days old pups of the alcoholic mother showed significant augmentation in CART-immunoreactivity in the cells of Edinger-Westphal (EW) nucleus and lateral hypothalamus. However, a significant decrease in CART-immunoreactivity was seen in nucleus accumbens shell (AcbSh), lateral part of bed nucleus of the stria terminalis (BNSTl), locus coeruleus (LC), hippocampus (CA1, CA2 and CA3), and arcuate nucleus (ARC) of the pups and/or adults offspring. While no change in the CART-immunoreactive fibers of AcbSh and BNSTl, CA2 and CA3 was noticed in the 25 days old pups, the CART-immunoreactive cells in EW and paraventricular nucleus (PVN), and fibers in the central nucleus of amygdala of 85 days old offspring remained unaffected. We suggest that the endogenous CART system in these discrete areas, among other factors, may be a causal to the abnormalities in the next generation of an alcoholic mother.

Keywords: anxiety, depression, CART, ethanol, immunocytochemistry

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Authors: Stephanie Hernández-Carreón, Judith Virginia Ríos-Arana

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Microplastics (MPs) are plastic particles smaller than 5 mm that has been detected in soil, air, organisms, and mostly water around the world. Most studies have focused on MPs detection in marine waters, and less so in freshwater, such is the case of Mexico, where studies about MPs in freshwaters are limited. One of the most important rivers in the country is The Rio Grande/Río Bravo, a natural border between Mexico and the United States. Its waters serve different purposes, such as fishing, habitat to endemic species, electricity generation, agriculture, and drinking water sources, among others. Despite its importance, the river’s waters have not been analyzed to determine the presence of MPs; therefore, the purpose of this research is to determine if the Rio Bravo/Rio Grande is polluted with microplastics. For doing so, three sites (Borderland, Casa de Adobe, and Guadalupe) along the El Paso-Juárez metroplex have been sampled: 30 L of water were filtered through a plankton net (64 µm) in each site and sediments-composed samples were collected. Water samples and sediments were 1) digested with a hydrogen peroxide solution (30%), 2) resuspended in a calcium chloride solution (1.5 g/cm3) to separate MPs, and 3) filtered through a 0.45 µm nitrocellulose membrane. Processed water samples were dyed with Nile Red (1 mg/ml ethanol) and analyzed by fluorescence microscopy. Two water samples have been analyzed until January 2023: Casa de Adobe and Borderland finding a concentration of 5.67 particles/L and 5.93 particles/L, respectively. Three types of particles were observed: fibers, fragments, and films, fibers being the most abundant. These data, as well as the data obtained from the rest of the samples, will be analyzed by an ANOVA (α=0.05). The concentrations and types of particles found in the Río Bravo correspond with other studies on rivers associated with urban environments and agricultural activities in China, where a range of 3.67—10.7 particles/L was reported in the Wei River. Even though we are in the early stages of the study, and three new sites will be sampled and analyzed in 2023 to provide more data about this issue in the river, this presents the first evidence of microplastic pollution in the Rio Grande.

Keywords: microplastics, fresh water, Rio Bravo, fluorescence microscopy

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Authors: Marriette Sakah, Samuel Gyamfi, Morkporkpor Delight Sedzro, Christoph Kuhn

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Ghana is experiencing rapid economic development and its cities command an increasingly dominant role as centers of both production and consumption. Cities run on energy and are extremely vulnerable to energy scarcity, energy price escalations and health impacts of very poor air quality. The overriding concern in Ghana and other West African states is bridging the gap between energy demand and supply. Energy efficiency presents a cost-effective solution for supply challenges by enabling more coverage with current power supply levels and reducing the need for investment in additional generation capacity and grid infrastructure. In Ghana, major issues for energy policy formulation in residential applications include lack of disaggregated electrical energy consumption data and lack of thorough understanding with regards to socio-economic influences on energy efficiency investment. This study uses a bottom up approach to estimate baseline electricity end-use as well as the energy consumption of best available technologies to enable estimation of energy-efficiency resource in terms of relative reduction in total energy use for Tema city, Ghana. A ground survey was conducted to assess the probable consumer behavior in response to energy efficiency initiatives to enable estimation of the amount of savings that would occur in response to specific policy interventions with regards to funding and incentives provision targeted at households. Results show that 16% - 54% reduction in annual electricity consumption is reasonably achievable depending on the level of incentives provision. The saved energy could supply 10000 - 34000 additional households if the added households use only best available technology. Political support and consumer awareness are necessary to translate energy efficiency resources into real energy savings.

Keywords: achievable energy savings, energy efficiency, Ghana, household appliances

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Authors: Juan A. G. Carrio, Prasad Talluri, Sergio G. Echeverrigaray, Antonio H. Castro Neto

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Hydrogen as a fuel and environmentally pleasant energy carrier is part of this transition towards low-carbon systems. The extensive deployment of hydrogen production, purification and transport infrastructures still represents significant challenges. Independent of the production process, the hydrogen generally is mixed with light hydrocarbons and other undesirable gases that need to be removed to obtain H₂ with the required purity for end applications. In this context, membranes are one of the simplest, most attractive, sustainable, and performant technologies enabling hydrogen separation and purification. They demonstrate high separation efficiencies and low energy consumption levels in operation, which is a significant leap compared to current energy-intensive options technologies. The unique characteristics of 2D laminates have given rise to a diversity of research on their potential applications in separation systems. Specifically, it is already known in the scientific literature that graphene oxide-based membranes present the highest reported selectivity of H₂ over other gases. This work explores the potential of a new type of 2D materials-based membranes in separating H₂ from CO₂ and CH₄. We have developed nanostructured composites based on 2D materials that have been applied in the fabrication of membranes to maximise H₂ selectivity and permeability, for different gas mixtures, by adjusting the membranes' characteristics. Our proprietary technology does not depend on specific porous substrates, which allows its integration in diverse separation modules with different geometries and configurations, looking to address the technical performance required for industrial applications and economic viability. The tuning and precise control of the processing parameters allowed us to control the thicknesses of the membranes below 100 nanometres to provide high permeabilities. Our results for the selectivity of new nanostructured 2D materials-based membranes are in the range of the performance reported in the available literature around 2D materials (such as graphene oxide) applied to hydrogen purification, which validates their use as one of the most promising next-generation hydrogen separation and purification solutions.

Keywords: membranes, 2D materials, hydrogen purification, nanocomposites

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Authors: Hamidreza Hoshyarmanesh, Sanju Lama, Garnette R. Sutherland

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In tele-operative robotic surgery, an ideal haptic device should be equipped with an intuitive and smooth end-effector to cover the surgeon’s hand/wrist degrees of freedom (DOF) and translate the hand joint motions to the end-effector of the remote manipulator with low effort and high level of comfort. This research introduces the design and development of a microsurgery-specific end-effector, a gimbal mechanism possessing 4 passive and 1 active DOFs, equipped with a bipolar forceps and haptic feedback. The robust gimbal structure is comprised of three light-weight links/joint, pitch, yaw, and roll, each consisting of low-friction support and a 2-channel accurate optical position sensor. The third link, which provides the tool roll, was specifically designed to grip the tool prongs and accommodate a low mass geared actuator together with a miniaturized capstan-rope mechanism. The actuator is able to generate delicate torques, using a threaded cylindrical capstan, to emulate the sense of pinch/coagulation during conventional microsurgery. While the tool left prong is fixed to the rolling link, the right prong bears a miniaturized drum sector with a large diameter to expand the force scale and resolution. The drum transmits the actuator output torque to the right prong and generates haptic force feedback at the tool level. The tool is also equipped with a hall-effect sensor and magnet bar installed vis-à-vis on the inner side of the two prongs to measure the tooltip distance and provide an analogue signal to the control system. We believe that such a haptic end-effector could significantly increase the accuracy of telerobotic surgery and help avoid high forces that are known to cause bleeding/injury.

Keywords: end-effector, force generation, haptic interface, robotic surgery, surgical tool, tele-operation

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Authors: Salsabila Meutia Meutia

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Indonesia as one of the countries that agreed to SDG's must commit to achieve this SDG's goal until the deadline of 2030. The government has tried hard to realize all the goals in the SDG’s, but there is still something that has not been achieved, especially the goal in number 4 which is to ensure that every human being has a decent and inclusive education and encourages lifelong learning opportunities for everyone. Teenagers who are the golden generation for Indonesia are starting to feel dependent on Youtube. The addictive virus of teenagers about using YouTube is both good news and bad news for the sustainability of government programs in achieving goals in SDG’s, especially in term of education. One popular YouTube channel among high school teenagers is Nihongo Mantappu which has 1.8 million followers. This channel contains interesting but quality content that can have a positive influence for the audience. This research was conducted to determine the effectiveness of the Nihongo Mantappu channel on Youtube as a means of fostering enthusiasm and awareness of learning in tenth graders of SMA Muhammadiyah 10 GKB, as well as how it affected in achieving quality educational goals as an effort to succeed in the Sustainable Development Goals of 2030. The objectives of this study were carried out with distributing questionnaires to tenth graders of SMA Muhammadiyah 10 GKB and observing objects in the real life. Then the data obtained are analyzed and described properly so that this research is a descriptive study. The results of the study mentioned that YouTube as one of the websites for viewing and sharing videos is a very effective media for disseminating information, especially among teenagers. The Nihongo Mantappu channel is also considered to be a very effective channel in building enthusiasm and awareness of learning in tenth graders of SMA Muhammadiyah 10 GKB. Students as the main subject of education have a great influence on the achievement of one of SDG’s fourth goals, named quality education. Students who are always on fire in the spirit and awareness of learning will greatly help the achievement of quality education goals in the Sustainable Development Goals by 2030.

Keywords: Youtube, Nihongo, Mantappu, SDG's

Procedia PDF Downloads 134

Authors: Viktor R. Stoynov, Zlatka V. Valkova-Jarvis

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The intelligent management and optimisation of radio resource technologies will lead to a considerable improvement in the overall performance in Next Generation Networks (NGNs). Carrier Aggregation (CA) technology, also known as Spectrum Aggregation, enables more efficient use of the available spectrum by combining multiple Component Carriers (CCs) in a virtual wideband channel. LTE-A (Long Term Evolution–Advanced) CA technology can combine multiple adjacent or separate CCs in the same band or in different bands. In this way, increased data rates and dynamic load balancing can be achieved, resulting in a more reliable and efficient operation of mobile networks and the enabling of high bandwidth mobile services. In this paper, several distinct CA deployment strategies for the utilisation of spectrum bands are compared in indoor-outdoor scenarios, simulated via the recently-developed Realistic Indoor Environment Generator (RIEG). We analyse the performance of the User Equipment (UE) by integrating the average throughput, the level of fairness of radio resource allocation, and other parameters, into one summative assessment termed a Comparative Factor (CF). In addition, comparison of non-CA and CA indoor mobile networks is carried out under different load conditions: varying numbers and positions of UEs. The experimental results demonstrate that the CA technology can improve network performance, especially in the case of indoor scenarios. Additionally, we show that an increase of carrier frequency does not necessarily lead to improved CF values, due to high wall-penetration losses. The performance of users under bad-channel conditions, often located in the periphery of the cells, can be improved by intelligent CA location. Furthermore, a combination of such a deployment and effective radio resource allocation management with respect to user-fairness plays a crucial role in improving the performance of LTE-A networks.

Keywords: comparative factor, carrier aggregation, indoor mobile network, resource allocation

Procedia PDF Downloads 178

Authors: D. Ramajo, S. Corzo, M. Nigro

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A Multi-dimensional computational fluid dynamics (CFD) two-phase model was developed with the aim to simulate the in-core coolant circuit of a pressurized heavy water reactor (PHWR) of a commercial nuclear power plant (NPP). Due to the fact that this PHWR is a Reactor Pressure Vessel type (RPV), three-dimensional (3D) detailed modelling of the large reservoirs of the RPV (the upper and lower plenums and the downcomer) were coupled with an in-house finite volume one-dimensional (1D) code in order to model the 451 coolant channels housing the nuclear fuel. Regarding the 1D code, suitable empirical correlations for taking into account the in-channel distributed (friction losses) and concentrated (spacer grids, inlet and outlet throttles) pressure losses were used. A local power distribution at each one of the coolant channels was also taken into account. The heat transfer between the coolant and the surrounding moderator was accurately calculated using a two-dimensional theoretical model. The implementation of subcooled boiling and condensation models in the 1D code along with the use of functions for representing the thermal and dynamic properties of the coolant and moderator (heavy water) allow to have estimations of the in-core steam generation under nominal flow conditions for a generic fission power distribution. The in-core mass flow distribution results for steady state nominal conditions are in agreement with the expected from design, thus getting a first assessment of the coupled 1/3D model. Results for nominal condition were compared with those obtained with a previous 1/3D single-phase model getting more realistic temperature patterns, also allowing visualize low values of void fraction inside the upper plenum. It must be mentioned that the current results were obtained by imposing prescribed fission power functions from literature. Therefore, results are showed with the aim of point out the potentiality of the developed model.

Keywords: PHWR, CFD, thermo-hydraulic, two-phase flow

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Authors: Bekir Turedi

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Exploiting the potential of perovskite single-crystal solar cells in optoelectronic applications necessitates overcoming a significant challenge: the low charge collection efficiency at increased thickness, which has restricted their deployment in radiation detectors and nuclear batteries. Our research details a promising approach to this problem, wherein we have successfully fabricated single-crystal MAPbI3 solar cells employing a space-limited inverse temperature crystallization (ITC) methodology. Remarkably, these cells, up to 400-fold thicker than current-generation perovskite polycrystalline films, maintain a high charge collection efficiency even without external bias. The crux of this achievement lies in the long electron diffusion length within these cells, estimated to be around 0.45 mm. This extended diffusion length ensures the conservation of high charge collection and power conversion efficiencies, even as the thickness of the cells increases. Fabricated cells at 110, 214, and 290 µm thickness manifested power conversion efficiencies (PCEs) of 20.0, 18.4, and 14.7% respectively. The single crystals demonstrated nearly optimal charge collection, even when their thickness exceeded 200 µm. Devices of thickness 108, 214, and 290 µm maintained 98.6, 94.3, and 80.4% of charge collection efficiency relative to their maximum theoretical short-circuit current value, respectively. Additionally, we have proposed an innovative, self-consistent technique for ascertaining the electron-diffusion length in perovskite single crystals under operational conditions. The computed electron-diffusion length approximated 446 µm, significantly surpassing previously reported values for this material. In conclusion, our findings underscore the feasibility of fabricating halide perovskite single-crystal solar cells of hundreds of micrometers in thickness while preserving high charge extraction efficiency and PCE. This advancement paves the way for developing perovskite-based optoelectronics necessitating thicker active layers, such as X-ray detectors and nuclear batteries.

Keywords: perovskite, solar cell, single crystal, diffusion length

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Authors: Yasir Ali Soomro

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Companies that demonstrate corporate social responsibilities (CSR) are more likely to withstand any downturn or crises because of the trust built with stakeholders. Many firms are utilizing CSR marketing to improve the interactions with their various stakeholders, mainly the consumers. Most previous research on CSR has focused on the impact of CSR on customer responses and behaviors toward a company. As online food ordering and grocery shopping remains inevitable. This study will investigate structural relationships among consumer positive emotions (CPE) and negative emotions (CNE), Corporate Reputation (CR), Customer Trust (CT), Brand Image (BI), and Brand attitude (BA) on behavioral outcomes such as Online purchase intention (OPI) and Word of mouth (WOM) in retail grocery and food restaurants setting. Hierarchy of Effects Model will be used as theoretical, conceptual framework. The model describes three stages of consumer behavior: (i) cognitive, (ii) affective, and (iii) conative. The study will apply a quantitative method to test the hypotheses; a self-developed questionnaire with non-probability sampling will be utilized to collect data from 500 consumers belonging to generation X, Y, and Z residing in KSA. The study will contribute by providing empirical evidence to support the link between CSR and customer affective and conative experiences in Saudi Arabia. The theoretical contribution of this study will be empirically tested comprehensive model where CPE, CNE, CR, CT, BI, and BA act as mediating variables between the perceived CSR & Online purchase intention (OPI) and Word of mouth (WOM). Further, the study will add more to how the emotional/ psychological process mediates in the CSR literature, especially in the Middle Eastern context. The proposed study will also explain the effect of perceived CSR marketing initiatives directly and indirectly on customer behavioral responses.

Keywords: corporate social responsibility, corporate reputation, consumer emotions, loyalty, online purchase intention, word-of-mouth, structural equation modeling

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Authors: Yi-Shiuan Chiu

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Deaf signers have been found to have better mental image performance than hearing nonsigners. The goal of this study was to investigate the ability to generate mental images, to maintain them, and to manipulate them in deaf signers of Taiwanese Sign Language (TSL). In the visual image task, participants first memorized digits formed in a cell of 4 × 5 grids. After presenting a cue of Chinese digit character shown on the top of a blank cell, participants had to form a corresponding digit. When showing a probe, which was a grid containing a red circle, participants had to decide as quickly as possible whether the probe would have been covered by the mental image of the digit. The ISI (interstimulus interval) between cue and probe was manipulated. In experiment 1, 24 deaf signers and 24 hearing nonsigners were asked to perform image generation tasks (ISI: 200, 400 ms) and image maintenance tasks (ISI: 800, 2000 ms). The results showed that deaf signers had had an enhanced ability to generate and maintain a mental image. To explore the process of mental image, in experiment 2, 30 deaf signers and 30 hearing nonsigners were asked to do visual searching when maintaining a mental image. Between a digit image cue and a red circle probe, participants were asked to search a visual search task to see if a target triangle apex was directed to the right or left. When there was only one triangle in the searching task, the results showed that both deaf signers and hearing non-signers had similar visual searching performance in which the searching targets in the mental image locations got facilitates. However, deaf signers could maintain better and faster mental image performance than nonsigners. In experiment 3, we increased the number of triangles to 4 to raise the difficulty of the visual search task. The results showed that deaf participants performed more accurately in visual search and image maintenance tasks. The results suggested that people may use eye movements as a mnemonic strategy to maintain the mental image. And deaf signers had enhanced abilities to resist the interference of eye movements in the situation of fewer distractors. In sum, these findings suggested that deaf signers had enhanced mental image processing.

Keywords: deaf signers, image maintain, mental image, visual search

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Authors: Gulnaz Erkomaishvili

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Introduction. One of the most important issues of state economic policy in the 21st century is the problem of environmental protection. The Georgian government considers the green economy as one of the most important means of sustainable economic development and takes the initiative to implement voluntary measures to promote sustainable development. In this context, it is important to promote the development of ecosystem services, clean production, environmental education and green jobs.The development of the green economy significantly reduces the inefficient use of natural resources, waste generation, emissions into the atmosphere and the discharge of untreated water into bodies of water.It is, therefore, an important instrument in the environmental orientation of sustainable development. Objectives.The aim of the paper is to analyze the current status of the green economy in Georgia and identify effective ways to improve the environmental, economic policy of sustainable development. Methodologies: This paper uses general and specific methods, in particular, analysis, synthesis, induction, deduction, scientific abstraction, comparative and statistical methods, as well as experts’ evaluation. bibliographic research of scientific works and reports of organizations was conducted; Publications of the National Statistics Office of Georgia are used to determine the regularity between analytical and statistical estimations. Also, theoretical and applied research of international organizations and scientist-economists are used. Contributions: The country should implement such an economic policy that ensures the transition to a green economy, in particular, revising water, air and waste laws, strengthening existing environmental management tools and introcing new tools (including economic tools). Perfecting the regulatory legal framework of the environmental impact assessment system, which includes the harmonization of Georgian legislation with the requirements of the European Union. To ensure the protection and rational use of Georgia's forests, emphasis should be placed on sustainable forestry, protection and restoration of forests.

Keywords: green economy, environmental protection, environmental protection economic policy, environmental protection policy challanges

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Authors: Yoftahe Nigussie Worku

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This report unveils a meticulous project focused on the design intricacies of a Fire Tube Boiler tailored for the efficient generation of saturated steam. The overarching objective is to produce 2000kg/h of saturated steam at 12-bar design pressure, achieved through the development of an advanced fire tube boiler. This design is meticulously crafted to harmonize cost-effectiveness and parameter refinement, with a keen emphasis on material selection for component parts, construction materials, and production methods throughout the analytical phases. The analytical process involves iterative calculations, utilizing pertinent formulas to optimize design parameters, including the selection of tube diameters and overall heat transfer coefficients. The boiler configuration incorporates two passes, a strategic choice influenced by tube and shell size considerations. The utilization of heavy oil fuel no. 6, with a higher heating value of 44000kJ/kg and a lower heating value of 41300kJ/kg, results in a fuel consumption of 140.37kg/hr. The boiler achieves an impressive heat output of 1610kW with an efficiency rating of 85.25%. The fluid flow pattern within the boiler adopts a cross-flow arrangement strategically chosen for inherent advantages. Internally, the welding of the tube sheet to the shell, secured by gaskets and welds, ensures structural integrity. The shell design adheres to European Standard code sections for pressure vessels, encompassing considerations for weight, supplementary accessories (lifting lugs, openings, ends, manhole), and detailed assembly drawings. This research represents a significant stride in optimizing fire tube boiler technology, balancing efficiency and safety considerations in the pursuit of enhanced saturated steam production.

Keywords: fire tube, saturated steam, material selection, efficiency

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Authors: Maria Ashitko

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The Constitution of the Republic of Belarus is based on the principle of the unity of rights and obligations, including those of the child. The constitutional status of the child is aspecific system of constitutional elements established and guaranteed by the state through the current legislation and regulatory acts that ensure the special legal status of the child, his or her constitutional legal capacity, implementation of the principles of the constitutional and legal status of the child, constitutional rights of the child and their safeguards. Under the principles of the constitutional status of the child, we consider the general, normative, social-volitional rules of behavior established by the Constitution of the Republic of Belarus, laws and other regulatory acts that determine the content and social purpose of the legal status of the child. The constitutional and legal status of the child is characterized by the following special principles, which form a feature of the state legal system:1) Ensuring the interests of the child means providing for the child in accordance with his or her age, state of health, characteristics of development, life experience, family life, cultural traditions, ethnicity. 2) The principle of equal responsibility of both parents or their substitutes characterized by caring for the next generation as one of the priority tasks of the state and society, and all issues related to the implementation of children’s rights should be addressed at the constitutional level. 3) We would like to highlight such a special principle as the subprinciple of safeguards, which is the principle of ensuring the safety of the child. It is also worth noting that in legal studies, there is no relationship between safety and constitutional rights as general safeguards of individual rights and freedoms, and as special safeguards for the right to life. 4) The principle of justice is expressed by the fact that in modern conditions, the quality of life is determined not only by material wealth but also by the ability of the state to ensure the harmonization of social relations and social harmony on the basis of humanism and justice. Thus, the specificity of the constitutional status of the child is the age boundary between adulthood and minority; therefore, we propose to highlight the age characteristics of the child as an additional element. It is advisable to highlight such a special principle as the subprinciple of safeguards, which is the principle of ensuring the safety of the child.

Keywords: children’s rights, constitutional status, constitutional principles, constitutional rights

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Authors: Fares A. Mayia, Mahmoud A. Yamany, Mushabbab A. Asiri

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In recent years, non-invasive Focused Ultrasound (FU) has been utilized for generating bubbles (cavities) to ablate target tissue by mechanical fractionation. Intensities >10 kW/cm² are required to generate the inertial cavities. The generation, rapid growth, and collapse of these inertial cavities cause tissue fractionation and the process is called Histotripsy. The ability to fractionate tissue from outside the body has many clinical applications including the destruction of the tumor mass. The process of tissue fractionation leaves a void at the treated site, where all the affected tissue is liquefied to particles at sub-micron size. The liquefied tissue will eventually be absorbed by the body. Histotripsy is a promising non-invasive treatment modality. This paper presents a technique for generating inertial cavities at lower intensities (< 1 kW/cm²). The technique (patent pending) is based on amplitude modulation (AM), whereby a low frequency signal modulates the amplitude of a higher frequency FU wave. Cavitation threshold is lower at low frequencies; the intensity required to generate cavitation in water at 10 kHz is two orders of magnitude lower than the intensity at 1 MHz. The Amplitude Modulation technique can operate in both continuous wave (CW) and pulse wave (PW) modes, and the percentage modulation (modulation index) can be varied from 0 % (thermal effect) to 100 % (cavitation effect), thus allowing a range of ablating effects from Hyperthermia to Histotripsy. Furthermore, changing the frequency of the modulating signal allows controlling the size of the generated cavities. Results from in vitro work demonstrate the efficacy of the new technique in fractionating soft tissue and solid calcium carbonate (Chalk) material. The technique, when combined with MR or Ultrasound imaging, will present a precise treatment modality for ablating diseased tissue without affecting the surrounding healthy tissue.

Keywords: focused ultrasound therapy, histotripsy, inertial cavitation, mechanical tissue ablation

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Authors: Archana Soni, Arvind Mittal, Manmohan Kapshe

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Energy has been recognized as one of the key inputs for the economic growth and social development of a country. High economic growth naturally means a high level of energy consumption. However, in the present energy scenario where there is a wide gap between the energy generation and energy consumption, it is extremely difficult to match the demand with the supply. India being one of the largest and rapidly growing developing countries, there is an impending energy crisis which requires immediate measures to be adopted. In this situation, the concept of Energy Intensity comes under special focus to ensure energy security in an environmentally sustainable way. Energy Intensity is defined as the energy consumed per unit output in the context of industrial energy practices. It is a key determinant of the projections of future energy demands which assists in policy making. Energy Intensity is inversely related to energy efficiency; lesser the energy required to produce a unit of output or service, the greater is the energy efficiency. Energy Intensity of Indian manufacturing industries is among the highest in the world and stands for enormous energy consumption. Hence, reducing the Energy Intensity of Indian manufacturing industries is one of the best strategies to achieve a low level of energy consumption and conserve energy. This study attempts to analyse the factors which influence the Energy Intensity of Indian manufacturing firms and how they can be used to reduce the Energy Intensity. The paper considers six of the largest energy consuming manufacturing industries in India viz. Aluminium, Cement, Iron & Steel Industries, Textile Industries, Fertilizer and Paper industries and conducts a detailed Energy Intensity analysis using the data from PROWESS database of the Centre for Monitoring Indian Economy (CMIE). A total of twelve independent explanatory variables based on various factors such as raw material, labour, machinery, repair and maintenance, production technology, outsourcing, research and development, number of employees, wages paid, profit margin and capital invested have been taken into consideration for the analysis.

Keywords: energy intensity, explanatory variables, manufacturing industries, PROWESS database

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Authors: Sherif Fayez Lewis Ghaly

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up to datefacupupdated planning has the mission of designing merchandise, plant life, procedures, enterprise, regions, and the development of a up to date. The requirements for up-to-date planning and the constructing of a updated have changed in recent years. everyday restructuring is turning inupupdated greater essential up-to-date hold the competitiveness of a manufacturing facilityupdated. restrictions in new regions, shorter existence cycles of product and manufacturing generation up-to-date a VUCA global (Volatility, Uncertainty, Complexity & Ambiguity) up-to-date greater frequent restructuring measures inside a manufacturing facilityupdated. A virtual up-to-date model is the making plans basis for rebuilding measures and up-to-date an fundamental up-to-date. short-time period rescheduling can now not be handled through on-web site inspections and manual measurements. The tight time schedules require 3177227fc5dac36e3e5ae6cd5820dcaa making plans fashions. updated the high variation fee of facup-to-dateries defined above, a method for rescheduling facupdatedries on the idea of a modern-day digital up to datery dual is conceived and designed for sensible software in updated restructuring projects. the point of interest is on rebuild approaches. The purpose is up-to-date preserve the planning basis (virtual up-to-date model) for conversions within a up to datefacupupdated updated. This calls for the application of a methodology that reduces the deficits of present techniques. The goal is up-to-date how a digital up to datery version may be up to date up to date during ongoing up to date operation. a method up-to-date on phoup to dategrammetry technology is presented. the focus is on developing a easy and fee-powerful up to date tune the numerous adjustments that arise in a manufacturing unit constructing in the course of operation. The method is preceded with the aid of a hardware and software assessment up-to-date become aware of the most cost effective and quickest version.

Keywords: building information modeling, digital factory model, factory planning, maintenance digital factory model, photogrammetry, restructuring

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Authors: Andrew R. Willis, Kevin Brink, Kathleen Dipple

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This article describes a software package called ROS-georegistration intended for use with the robot operating system (ROS) and the Gazebo 3D simulation environment. ROSgeoregistration provides tools for the simulation, test, and deployment of aerial georegistration algorithms and is available at github.com/uncc-visionlab/rosgeoregistration. A model creation package is provided which downloads multi-spectral images from the Google Earth Engine database and, if necessary, incorporates these images into a single, possibly very large, reference image. Additionally a Gazebo plugin which uses the real-time sensor pose and image formation model to generate simulated imagery using the specified reference image is provided along with related plugins for UAV relevant data. The novelty of this work is threefold: (1) this is the first system to link the massive multi-spectral imaging database of Google’s Earth Engine to the Gazebo simulator, (2) this is the first example of a system that can simulate geospatially and radiometrically accurate imagery from multiple sensor views of the same terrain region, and (3) integration with other UAS tools creates a new holistic UAS simulation environment to support UAS system and subsystem development where real-world testing would generally be prohibitive. Sensed imagery and ground truth registration information is published to client applications which can receive imagery synchronously with telemetry from other payload sensors, e.g., IMU, GPS/GNSS, barometer, and windspeed sensor data. To highlight functionality, we demonstrate ROSgeoregistration for simulating Electro-Optical (EO) and Synthetic Aperture Radar (SAR) image sensors and an example use case for developing and evaluating image-based UAS position feedback, i.e., pose for image-based Guidance Navigation and Control (GNC) applications.

Keywords: EO-to-EO, EO-to-SAR, flight simulation, georegistration, image generation, robot operating system, vision-based navigation

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Authors: Farzaneh Tahmoorian, Bijan Samali, John Yeaman

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Road networks are expanding all over the world during the past few decades to meet the increasing freight volumes created by the population growth and industrial development. At the same time, the rate of generation of solid wastes in the society is increasing with the population growth, technological development, and changes in the lifestyle of people. Thus, the management of solid wastes has become an acute problem. Accordingly, there is a need for greater efficiency in the construction and maintenance of road networks, in reducing the overall cost, especially the utilization of natural materials such as aggregates. An efficient means to reduce construction and maintenance costs of road networks is to replace natural (virgin) materials by secondary, recycled materials. Recycling will also help to reduce pressure on landfills and demand for extraction of natural virgin materials thus ensuring sustainability. Application of solid wastes in asphalt layer reduces not only environmental issues associated with waste disposal but also the demand for virgin materials which will subsequently result in sustainability. Therefore, this research aims to investigate the feasibility of the application of some of the waste materials such as glass, construction and demolition wastes, etc. as alternative materials in pavement construction, particularly flexible pavements. To this end, various combination of different waste materials in certain percentages is considered in designing the asphalt mixture. One of the goals of this research is to determine the optimum percentage of all these materials in the mixture. This is done through a series of tests to evaluate the volumetric properties and resilient modulus of the mixture. The information and data collected from these tests are used to select the adequate samples for further assessment through advanced tests such as triaxial dynamic test and fatigue test, in order to investigate the asphalt mixture resistance to permanent deformation and also cracking. This paper presents the results of these investigations on the application of waste materials in asphalt mixture for production of a sustainable asphalt mix.

Keywords: asphalt, glass, pavement, recycled aggregate, sustainability

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Authors: T. Kuchukhidze, N. Jalagonia, Z. Phachulia, R. Chedia

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Ceramic obtained on the base of aluminum oxide has wide application range, because it has unique properties, for example, wear-resistance, dielectric characteristics, exploitation ability at high temperatures and in corrosive atmosphere. Low temperature synthesis of α-Al2O3 is energo-economical process and it is actual for developing technologies of corundum ceramics fabrication. In the present work possibilities of low temperature transformation of oxyhydroxides in α-Al2O3, during a presence of small amount of rare–earth elements compounds (also Th, Re), have been discussed. Aluminium unstable oxyhydroxides have been obtained by hydrolysis of aluminium isopropoxide, nitrates, sulphate, chloride in alkaline environment at 80-90ºC tempertures. β-Al(OH)3 has been received from aluminium powder by ultrasonic development. Drying of oxyhydroxide sol has been conducted with presence of various types seeds, which amount reaches 0,1-0,2% (mas). Neodymium, holmium, thorium, lanthanum, cerium, gadolinium, disprosium nitrates and rhenium carbonyls have been used as seeds and they have been added to the sol specimens in amount of 0.1-0.2% (mas) calculated on metals. Annealing of obtained gels is carried out at 70 – 1100ºC for 2 hrs. The same specimen transforms in α-Al2O3 at 1100ºC. At this temperature in case of presence of lanthanum and gadolinium transformation takes place by 70-85%. In case of presence of thorium stabilization of γ-and θ-phases takes place. It is established, that thorium causes inhibition of α-phase generation at 1100ºC, at the time in all other doped specimens α-phase is generated at lower temperatures (1000-1050ºC). During the work the following devices have been used: X-ray difractometer DRON-3M (Cu-Kα, Ni filter, 2º/min), High temperature vacuum furnace OXY-GON, electronic scanning microscopes Nikon ECLIPSE LV 150, NMM-800TRF, planetary mill Pulverisette 7 premium line, SHIMADZU Dynamic Ultra Micro Hardness Tester, DUH-211S, Analysette 12 Dyna sizer.

Keywords: α-Alumina, combustion, phase transformation, seeding

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Authors: Aimen Saleh

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The Silurian Lower Acacus sandstone is one of the main reservoirs in North West Libya. Our aim in this study is to grasp a robust understanding of the hydrocarbon potential and distribution in the area. To date, the depositional environment of the Lower Acacus reservoir still open to discussion and contradiction. Henceforth, building three dimensional (3D) property modelling is one way to support the analysis and description of the reservoir, its properties and characterizations, so this will be of great value in this project. The 3D model integrates different data set, these incorporates well logs data, petrophysical reservoir properties and seismic data as well. The finalized depositional environment model of the Lower Acacus concludes that the area is located in a deltaic transitional depositional setting, which ranges from a wave dominated delta into tide dominated delta type. This interpretation carried out through a series of steps of model generation, core description and Formation Microresistivity Image tool (FMI) interpretation. After the analysis of the core data, the Lower Acacus layers shows a strong effect of tidal energy. Whereas these traces found imprinted in different types of sedimentary structures, for examples; presence of some crossbedding, such as herringbones structures, wavy and flaser cross beddings. In spite of recognition of some minor marine transgression events in the area, on the contrary, the coarsening upward cycles of sand and shale layers in the Lower Acacus demonstrate presence of a major regressive phase of the sea level. However, consequently, we produced a final package of this model in a complemented set of facies distribution, porosity and oil presence. And also it shows the record of the petroleum system, and the procedure of Hydrocarbon migration and accumulation. Finally, this model suggests that the area can be outlined into three main segments of hydrocarbon potential, which can be a textbook guide for future exploration and production strategies in the area.

Keywords: Acacus, Ghadames , Libya, Silurian

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Authors: Nakul V. Naphade, Sandra G. L. Persiani, Yew Wah Wong, Pramod S. Kamath, Avinash H. Anantharam, Hui Ling Aw, Yann Grynberg

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Achieving zero-energy targets in existing buildings is known to be a difficult task requiring important cuts in the building energy consumption, which in many cases clash with the functional necessities of the building wherever the on-site energy generation is unable to match the overall energy consumption. Between the building’s consumption optimization limit and the energy, target stretches a case-specific optimization grey zone, which requires tailored intervention and enhanced user’s commitment. In the view of the future adoption of more stringent energy-efficiency targets in the context of hot-humid tropical climates, this study aims to define the energy optimization grey zone by assessing the energy-efficiency limit in the state-of-the-art typical mid- and high-rise full AC office buildings, through the integration of currently available technologies. Energy models of two code-compliant generic office-building typologies were developed as a baseline, a 20-storey ‘high-rise’ and a 7-storey ‘mid-rise’. Design iterations carried out on the energy models with advanced market ready technologies in lighting, envelope, plug load management and ACMV systems and controls, lead to a representative energy model of the current maximum technical potential. The simulations showed that ZEB targets could be achieved in fully AC buildings under an average of seven floors only by compromising on energy-intense facilities (as full AC, unlimited power-supply, standard user behaviour, etc.). This paper argues that drastic changes must be made in tropical buildings to span the energy optimization grey zone and achieve zero energy. Fully air-conditioned areas must be rethought, while smart technologies must be integrated with an aggressive involvement and motivation of the users to synchronize with the new system’s energy savings goal.

Keywords: energy simulation, office building, tropical climate, zero energy buildings

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Authors: Priyanka Dargode, Suhas Gore, Manju Sharma, Arvind Lali

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Anaerobic digestion has been widely used for production of methane from different biowastes. However, the complexity of microbial communities involved in the process is poorly understood. The performance of biogas production process concerning the process productivity is closely coupled to its microbial community structure and syntrophic interactions amongst the community members. The present study aims at understanding taxonomic variations occurring in any starter inoculum when acclimatised to different lignocellulosic biomass (LBM) feedstocks relating to time of digestion. The work underlines use of high throughput Next Generation Sequencing (NGS) for validating the changes in taxonomic patterns of microbial communities. Biomethane Potential (BMP) batches were set up with different pretreated and non-pretreated LBM residues using the same microbial consortium and samples were withdrawn for studying the changes in microbial community in terms of its structure and predominance with respect to changes in metabolic profile of the process. DNA of samples withdrawn at different time intervals with reference to performance changes of the digestion process, was extracted followed by its 16S rRNA amplicon sequencing analysis using Illumina Platform. Biomethane potential and substrate consumption was monitored using Gas Chromatography(GC) and reduction in COD (Chemical Oxygen Demand) respectively. Taxonomic analysis by QIIME server data revealed that microbial community structure changes with different substrates as well as at different time intervals. It was observed that biomethane potential of each substrate was relatively similar but, the time required for substrate utilization and its conversion to biomethane was different for different substrates. This could be attributed to the nature of substrate and consequently the discrepancy between the dominance of microbial communities with regards to different substrate and at different phases of anaerobic digestion process. Knowledge of microbial communities involved would allow a rational substrate specific consortium design which will help to reduce consortium adaptation period and enhance the substrate utilisation resulting in improved efficacy of biogas process.

Keywords: amplicon sequencing, biomethane potential, community predominance, taxonomic analysis

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Authors: Ibrahim Darwish, Noora Abu Ain

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Referring to female relatives by male Jordanian speakers in public is governed by various linguistic and social constraints. Although Jordanian society is less conservative than it was a few decades ago, women are still considered the weaker link in society and men still believe that they need to protect them. Conservative Jordanians often avoid referring to their female relatives overtly, i.e., using their real names. Instead, they use covert names, such as pseudonyms, nicknames, pet names, etc. The reason behind such language use has to do with how Arab men, in general, see women as part of their honor. This study intends to investigate to what extent Jordanian males hide their female relatives’ names in public domains. The data was collected from spontaneous informal voice-recorded interviews carried out in the village of Saham in the far north of Jordan. Saham’s dialect is part of a larger Horani dialect used by speakers along a wide area that stretches from Salt in the south to the Syrian borders in the north of Jordan. The voice-recorded interviews were originally carried out as an audio record of some customs and traditions in the village of Saham in 2013. During most of these interviews, the researchers observed how the male participants indirectly referred to their female relatives. Instead of using real names, the male speakers used broad terms to refer to their female relatives, such al-Beit ‘the home,’ al-ciyaal ‘the kids’, um-x ‘the mother of x,’ etc. All tokens related to the issue in question were collected, analyzed and quantified about three age cohorts: young, middle-aged and old speakers. The results show that young speakers are more direct in referring to their female relatives than the other two age groups. This can point to a possible change in progress in the speech community of Saham. It is argued that due to contact with other urban speech communities, the young speakers in Saham do not feel the need to hide the real names of their female relatives as they consider them as equals. Indeed, the young generation is more open to the idea of women's rights and call for expanding Jordanian women’s roles in Jordanian society.

Keywords: gender differences, Horan, proper names, social constraints

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Authors: Koko Iwan Agus Kurniawan, Dwi Purnomo, Anas Bunyamin, Arif Rahman Jaya

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Fruters model is a concept of technopreneurship-based on empowerment, in which technology research results were designed to create high value-added products and implemented as a locomotive of collaborative empowerment; thereby, the impact was widely spread. This model still needs to be inventoried and validated concerning the influenced variables in the business growth process. Model validation accompanied by mapping was required to be applicable to Small Medium Enterprises (SMEs) agro-industry based on sustainable social business and existing real cases. This research explained the empowerment model of Yourgood, an SME, which emphasized on empowering the farmers/ breeders in farmers in rural areas, Cipageran, Cimahi, to housewives in urban areas, Bandung, West Java, Indonesia. This research reviewed some works of literature discussing the agro-industrial development associated with the empowerment and social business process and gained a unique business model picture with the social business platform as well. Through the mapped business model, there were several advantages such as technology acquisition, independence, capital generation, good investment growth, strengthening of collaboration, and improvement of social impacts that can be replicated on other businesses. This research used analytical-descriptive research method consisting of qualitative analysis with design thinking approach and that of quantitative with the AHP (Analytical Hierarchy Process). Based on the results, the development of the enterprise’s process was highly affected by supplying farmers with the score of 0.248 out of 1, being the most valuable for the existence of the enterprise. It was followed by university (0.178), supplying farmers (0.153), business actors (0.128), government (0.100), distributor (0.092), techno-preneurship laboratory (0.069), banking (0.033), and Non-Government Organization (NGO) (0.031).

Keywords: agro-industry, small medium enterprises, empowerment, design thinking, AHP, business model canvas, social business

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Authors: Israel Ekanade, Richard Molapo, Patrick Dzimiri, Isaac Ndlovu

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This study aims to unravel the myth behind animosity towards foreign nationals in South Africa. Systemic violence against foreign African nationals since 2008 to date necessitates critical research with regards to migration issues connected to social upheavals. Extensive research ubiquitously tagged black-on-black violence as xenophobia or Afrophobia. In all, escalation of violence indicates a connotation of belonging. With unemployment rates approaching a crescendo, other vices have also soared in the same regard. As a result, this present generation seems cynical as the South African state has not fulfilled her obligations towards the indigent population; a situation pitching locals against foreigners. Locals have repeatedly blamed African foreign nationals for the economic downturn, using service delivery strikes to express their grievances. These strikes have continued unabatedly over the years but February 2017 marked a turning point in ‘insider-outsider’ relations as the strike was now turned to an anti-immigrant march resulting into widespread violence as the police failed to restore normalcy at some point. Over time, migration has been a harbinger of violence against the foreign black population in South Africa. Our paper encourages the state and civil society to invent new peace-building mechanisms to reduce xenophobic orchestrated violence. Our paper also contends that since the political class has hijacked the situation by using the youths for political propaganda during crises periods, a re-education of the political class and a culture of tolerance is inevitable for peace and harmony between locals and foreigners in post-apartheid South Africa.

Keywords: anti-immigrant march, politics of belonging, service delivery strikes, South Africa

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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