Search results for: customer information system

Authors: Kangana Sengar, Sanjay Deb, Ramesh Dawar

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Introduction: Ki-67 can be a useful marker in determining proliferative activity in patients with multiple myeloma (MM). However, using Ki-67 alone results in the erroneous inclusion of non-myeloma cells leading to false high counts. We have used Dual IHC (immunohistochemistry) staining with Ki-67 and CD138 to enhance specificity in assessing proliferative activity of bone marrow plasma cells. Aims and objectives: To estimate the proportion of proliferating (Ki-67 expressing) plasma cells in patients with MM and correlation of Ki-67 with other known prognostic parameters. Materials and Methods: Fifty FFPE (formalin fixed paraffin embedded) blocks of trephine biopsies of cases diagnosed as MM from 2010 to 2015 are subjected to H & E staining and Dual IHC staining for CD 138 and Ki-67. H & E staining is done to evaluate various histological parameters like percentage of plasma cells, pattern of infiltration (nodular, interstitial, mixed and diffuse), routine parameters of marrow cellularity and hematopoiesis. Clinical data is collected from patient records from Medical Record Department. Each of CD138 expressing cells (cytoplasmic, red) are scored as proliferating plasma cells (containing a brown Ki¬67 nucleus) or non¬proliferating plasma cells (containing a blue, counter-stained, Ki-¬67 negative nucleus). Ki-67 is measured as percentage positivity with a maximum score of hundred percent and lowest of zero percent. The intensity of staining is not relevant. Results: Statistically significant correlation of Ki-67 in D-S Stage (Durie & Salmon Stage) I vs. III (p=0.026) and ISS (International Staging System) Stage I vs. III (p=0.019), β2m (p=0.029) and percentage of plasma cells (p < 0.001) is seen. No statistically significant correlation is seen between Ki-67 and hemoglobin, platelet count, total leukocyte count, total protein, albumin, S. calcium, S. creatinine, S. LDH, blood urea and pattern of infiltration. Conclusion: Ki-67 index correlated with other known prognostic parameters. However, it is not determined routinely in patients with MM due to little information available regarding its relevance and paucity of studies done to correlate with other known prognostic factors in MM patients. To the best of our knowledge, this is the first study in India using Dual IHC staining for Ki-67 and CD138 in MM patients. Routine determination of Ki-67 will help to identify patients who may benefit with more aggressive therapy. Recommendation: In this study follow up of patients is not included, and the sample size is small. Studying with larger sample size and long follow up is advocated to prognosticate Ki-67 as a marker of survival in patients with multiple myeloma.

Keywords: bone marrow, dual IHC, Ki-67, multiple myeloma

Procedia PDF Downloads 130

Authors: Saroj Panthi, Sher Singh Thagunna

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Reliable and sufficient information regarding status, distribution and habitat preference of red panda (Ailurus fulgens fulgens) is lacking in Nepal. The research activities on red panda in the mid-western Nepal are very limited, so the status of red panda in the region is quite unknown. The study conducted during May, 2013 in three Village Development Committees (VDCs) namely Godhemahadev, Malikathata and Tamti of Jumla district was an important step for providing vital information including distribution and habitat preference of this species. The study included the reconnaissance, key informants survey, interviews, and consultation for the most potential area identification, opportunistic survey comprising the direct observation and indirect sign count method for the presence and distribution, habitat assessment consisting vegetation sampling and ocular estimation. The study revealed the presence of red panda in three forests namely Bahirepatan, Imilchadamar and Tyakot of Godhemahadev, Tamti and Malikathata VDCs respectively. The species was found distributed between 2880 and 3244 m with an average dropping encounter rate of 1.04 per hour of searching effort and 12 pellets per dropping. Red panda mostly preferred the habitat in the elevation range of 2900 - 3000 m with southwest facing steep slopes (36˚ - 45˚), associated with water sources at the distance of ≤100 m. Trees such as Acer spp., Betula utilis and Quercus semecarpifolia, shrub species of Elaeagnus parvifolia, Drepanostachyum spp. and Jasminum humile, and the herbs like Polygonatum cirrhifolium, Fragaria nubicola and Galium asperifolium were found to be the most preferred species by red panda. The red panda preferred the habitat with dense crown coverage ( >20% - 100%) and 31% - 50% ground cover. Fallen logs (39%) were the most preferred substrate used for defecation.

Keywords: distribution, habitat preference, jumla, red panda

Procedia PDF Downloads 301

Authors: Samaneh Khalili

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Natural law theory, in moral philosophy, refers to a system of unchanging values held to be mutual to all humans and can be discovered through reason. The natural law theory is commonly associated with western Philosophers. In contrast, discussions on notions of natural law in Islamic intellectual history were relatively rare. This paper aims to show that the moral theory developed by the Mu'tazilite thinkers can be classified in the ideas of natural law. In doing so, this study will demonstrate that the objective and unchanging values, according to Mu'tazilite theologians, provide the guidelines for assessing the Islamic law rules in the field of human coexistence. The focus of the paper lies on ʿAbd al-Ğabbār, who was the most influential thinker in the late epoch of the Muʿtazila. Although ʿAbd al-Ǧabbār did not leave a text with a systematic discussion of natural law, his teaching of nature, human reason, and the moral values of actions are all scattered throughout his work -'al-Muġnī fī abwāb at-tawḥīd wa-l-'adl'. It is necessary to focus on ʿAbd al-Ǧabbār's theories on reason, nature, and ethics since natural law revolves around the basic concepts of nature, reason, and moral value. While analyzing the concept of the Nature, it will attempt to answer how he explains the world's physical structure and God's relationship to natural events. Moreover, from ʿAbd al-Ǧabbār's point of view, is nature a self-determined system that follows its inner principle in every kind of change, or is nature guided by an external power? Does causality govern natural events? About the concept of reason, an attempt is made to examine how human reason, according to ʿAbd al-Ǧabbār, conceives moral attributes. Finally, the Autor will discuss the concepts of objective values and the place of rights and duties derived from Islamic law in ʿAbd al-Ǧabbār's thought.

Keywords: Islamic law, Mu'tazilite theology, natural law in Islamic theology, objective and unchanging values.

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Authors: Oliver Marunțălu, Elena Elisabeta Manea, Lăcrămioara Diana Robescu, Mihai Necșoiu, Gheorghe Lăzăroiu, Dana Andreya Bondrea

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In order to obtain efficient pollutants removal in small-scale wastewater treatment plants, uniform water flow has to be achieved. The experimental setup, designed for treating high-load wastewater (leachate), consists of two aerobic biological reactors and a lamellar settler. Both biological tanks were aerated by using three different types of aeration systems - perforated pipes, membrane air diffusers and tube ceramic diffusers. The possibility of homogenizing the water mass with each of the air diffusion systems was evaluated comparatively. The oxygen concentration was determined by optical sensors with data logging. The experimental data was analyzed comparatively for all three different air dispersion systems aiming to identify the oxygen concentration variation during different operational conditions. The Oxygenation Capacity was calculated for each of the three systems and used as performance and selection parameter. The global mass transfer coefficients were also evaluated as important tools in designing the aeration system. Even though using the tubular porous diffusers leads to higher oxygen concentration compared to the perforated pipe system (which provides medium-sized bubbles in the aqueous solution), it doesn’t achieve the threshold limit of 80% oxygen saturation in less than 30 minutes. The study has shown that the optimal solution for the studied configuration was the radial air diffusers which ensure an oxygen saturation of 80% in 20 minutes. An increment of the values was identified when the air flow was increased.

Keywords: flow, aeration, bioreactor, oxygen concentration

Procedia PDF Downloads 377

Authors: Dangut Maren David, Skaf Zakwan

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Adequate monitoring of vehicle component in other to obtain high uptime is the goal of predictive maintenance, the major challenge faced by businesses in industries is the significant cost associated with a delay in service delivery due to system downtime. Most of those businesses are interested in predicting those problems and proactively prevent them in advance before it occurs, which is the core advantage of Prognostic Health Management (PHM) application. The recent emergence of industry 4.0 or industrial internet of things (IIoT) has led to the need for monitoring systems activities and enhancing system-to-system or component-to- component interactions, this has resulted to a large generation of data known as big data. Analysis of big data represents an increasingly important, however, due to complexity inherently in the dataset such as imbalance classification problems, it becomes extremely difficult to build a model with accurate high precision. Data-driven predictive modeling for condition-based maintenance (CBM) has recently drowned research interest with growing attention to both academics and industries. The large data generated from industrial process inherently comes with a different degree of complexity which posed a challenge for analytics. Thus, imbalance classification problem exists perversely in industrial datasets which can affect the performance of learning algorithms yielding to poor classifier accuracy in model development. Misclassification of faults can result in unplanned breakdown leading economic loss. In this paper, an advanced approach for handling imbalance classification problem is proposed and then a prognostic model for predicting aircraft component replacement is developed to predict component replacement in advanced by exploring aircraft historical data, the approached is based on hybrid ensemble-based method which improves the prediction of the minority class during learning, we also investigate the impact of our approach on multiclass imbalance problem. We validate the feasibility and effectiveness in terms of the performance of our approach using real-world aircraft operation and maintenance datasets, which spans over 7 years. Our approach shows better performance compared to other similar approaches. We also validate our approach strength for handling multiclass imbalanced dataset, our results also show good performance compared to other based classifiers.

Keywords: prognostics, data-driven, imbalance classification, deep learning

Procedia PDF Downloads 158

Authors: Shabadini Sampath, Jinglang Feng

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With huge kinetic energy, space debris poses a major threat to astronauts’ space activities and spacecraft in orbit if a collision happens. The active removal of space debris is required in order to avoid frequent collisions that would occur. In addition, the amount of space debris will increase uncontrollably, posing a threat to the safety of the entire space system. But the safe and reliable removal of large-scale space debris has been a huge challenge to date. While capturing and deorbiting space debris, the space manipulator has to achieve high control precision. However, due to uncertainties and unknown disturbances, there is difficulty in coordinating the control of the space manipulator. To address this challenge, this paper focuses on developing a robust and intelligent control algorithm that controls joint movement and restricts it on the sliding manifold by reducing uncertainties. A neural network adaptive sliding mode controller (NNASMC) is applied with the objective of finding the control law such that the joint motions of the space manipulator follow the given trajectory. A computed torque control (CTC) is an effective motion control strategy that is used in this paper for computing space manipulator arm torque to generate the required motion. Based on the Lyapunov stability theorem, the proposed intelligent controller NNASMC and CTC guarantees the robustness and global asymptotic stability of the closed-loop control system. Finally, the controllers used in the paper are modeled and simulated using MATLAB Simulink. The results are presented to prove the effectiveness of the proposed controller approach.

Keywords: GNC, active removal of space debris, AI controllers, MatLabSimulink

Procedia PDF Downloads 116

Authors: Muhammad Nasar-u-Minallah, Dagmar Haase, Salman Qureshi

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Rapid urbanization significantly change land use, urban nature, land surface vegetation cover, and heat distribution, leading to the formation of urban heat island (UHI) effect and affecting the healthy growth of cities and the comfort of human living style. Past information and present changes in Land Surface Temperature (LST) and urban landscapes could be useful to geographers, environmentalists, and urban planners in an attempt to shape the urban development process and mitigate the effects of urban heat islands (UHI). This study aims at using Satellite Remote Sensing (SRS) and GIS techniques to develop an approach for assessing the urban nature and UHI effects in Lahore, Pakistan. The study employed the Radiative Transfer Method (RTM) in estimating LST to assess the SUHI effect during the interval of 20 years (2000-2020). The assessment was performed by the available Landsat 7/ETM+ and Landsat 8/OIL_TIRs data for the years 2000, 2010, and 2020 respectively. Pearson’s correlation and normalized mutual information were applied to investigate the relationship between green space characteristics and LST. The result of this work revealed that the influence of urban heat island is not always at the city centers but sometimes in the outskirt where a lot of development activities were going on towards the direction of expansion of Lahore, Pakistan. The present study explores the usage of image processing and spatial analysis in the drive towards achieving urban greening of Lahore and a sustainable urban environment in terms of urban planning, policy, and decision making and promoting the healthy and sustainable urban environment of the city.

Keywords: urban nature, urban heat islands, urban green space, land use, Lahore

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Authors: Noorulaine Maqsood, Saeed Khan

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Background: Concern regarding incident reporting and bio-safety training in clinical laboratories in Pakistan has increased remarkably in the last few years due to rapid increase in diagnosis and research on infectious organisms. In order to ensure the safety of employees, this issue needs to be addressed immediately. Bio-safety training sessions and lectures are necessary for the protection of laboratory workers in order to ensure safe practices and minimize the count of incident reporting in the lab. Objective: To carry out an inter-departmental survey in lab regarding the awareness of bio-safety practices among lab employees before and after conducting bio-safety training sessions. Methodology: We conducted a 30 questions survey of laboratory workers in June 2013 (before training session) to gather information related to bio-safety awareness. Afterwards, we conducted another survey after training sessions and workshops related to bio-safety. Result: The survey regarding bio-safety level showed that before the training session 32% of the participants were aware of bio-safety level being used in their lab whereas after the session this percentage increased to 72%. 48% of the participants had information about the proper usage of PPE which increased to 76%. Awareness regarding proper management of hazardous waste increased from 32% to 64%. The incident reporting practice, sample handling and hand hygiene awareness was previously reported to be 40%, 65%, and 52% that increased to 80%, 85% and 88% respectively after the training session was completed. Conclusion: The first survey results showed lack of awareness that suggest nearly all senior scientists, faculty, medical technologist, lab attendant and housekeeping staff working in laboratories are required to have bio-safety training, and required inspection at least twice a year by a bio-safety officer and also required to renew their bio-safety training. After the training session, significant changes in awareness level and attitude of the participants regarding biosafety practices were observed. Therefore, such bio-safety sessions should be carried out regularly in clinical laboratories.

Keywords: biosafety practices, clinical laboratory, Pakistan, survey

Procedia PDF Downloads 418

Authors: Jubaida Gulshan Ara, Zebun Nasreen Ahmed

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Urban flood and drought has been a major problem of Dhaka city, particularly in recent years. Continuous increase of the city built up area, and limiting rainwater infiltration zone, are thought to be the main causes of the problem. Proper rainwater management, even at the individual plot level, might bring significant improvement in this regard. As residential use pattern occupies a significant portion of the city surface, the scope of rainwater harvesting (RWH) in residential buildings can be investigated. This paper reports on a research which explored the scope of rainwater harvesting in residential plots, with multifamily apartment buildings, in Dhaka city. The research investigated the basics of RWH, contextual information, i.e., hydro-geological, meteorological data of Dhaka city and the rules and legislations for residential building construction. The study also explored contemporary rainwater harvesting practices in the local and international contexts. On the basis of theoretical understanding, 21 sample case-studies, in different phases of construction, were selected from seven different categories of plot sizes, in different residential areas of Dhaka city. Primary data from the 21 case-study buildings were collected from a physical survey, from design drawings, accompanied by a questionnaire survey. All necessary secondary data were gathered from published and other relevant sources. Collected primary and secondary data were used to calculate and analyze the RWH needs for each case study, based on the theoretical understanding. The main findings have been compiled and compared, to observe residential development trends with regards to building rainwater harvesting system. The study has found that, in ‘Multifamily Apartment Building’ of Dhaka city, storage, and recharge structure size for rainwater harvesting, increases along with occupants’ number, and with the increasing size of the plot. Hence, demand vs. supply ratio remains almost the same for different sizes of plots, and consequently, the size of the storage structure increases significantly, in large-scale plots. It has been found that rainwater can meet only 12%-30% of the total restricted water demand of these residential buildings of Dhaka city. Therefore, artificial groundwater recharge might be the more suitable option for RWH, than storage. The study came up with this conclusion that, in multifamily residential apartments of Dhaka city, artificial groundwater recharge might be the more suitable option for RWH, than storing the rainwater on site.

Keywords: Dhaka city, rainwater harvesting, residential plots, urban flood

Procedia PDF Downloads 175

Authors: E. Asadollahi-Yazdi, J. Gardan, P. Lafon

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Nowadays, manufactures are encountered with production of different version of products due to quality, cost and time constraints. On the other hand, Additive Manufacturing (AM) as a production method based on CAD model disrupts the design and manufacturing cycle with new parameters. To consider these issues, the researchers utilized Design For Manufacturing (DFM) approach for AM but until now there is no integrated approach for design and manufacturing of product through the AM. So, this paper aims to provide a general methodology for managing the different production issues, as well as, support the interoperability with AM process and different Product Life Cycle Management tools. The problem is that the models of System Engineering which is used for managing complex systems cannot support the product evolution and its impact on the product life cycle. Therefore, it seems necessary to provide a general methodology for managing the product’s diversities which is created by using AM. This methodology must consider manufacture and assembly during product design as early as possible in the design stage. The latest approach of DFM, as a methodology to analyze the system comprehensively, integrates manufacturing constraints in the numerical model in upstream. So, DFM for AM is used to import the characteristics of AM into the design and manufacturing process of a hybrid product to manage the criteria coming from AM. Also, the research presents an integrated design method in order to take into account the knowledge of layers manufacturing technologies. For this purpose, the interface model based on the skin and skeleton concepts is provided, the usage and manufacturing skins are used to show the functional surface of the product. Also, the material flow and link between the skins are demonstrated by usage and manufacturing skeletons. Therefore, this integrated approach is a helpful methodology for designer and manufacturer in different decisions like material and process selection as well as, evaluation of product manufacturability.

Keywords: additive manufacturing, 3D printing, design for manufacturing, integrated design, interoperability

Procedia PDF Downloads 302

Authors: Filip Buruiana, Alexander Hall, Reimar Hofmann, Thomas Hofmann, Silviu Ganceanu, Alexandru Tudorica

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In-memory column-stores make interactive analysis feasible for many big data scenarios. PowerDrill is a system used internally at Google for exploration in logs data. Even though it is a highly parallelized column-store and uses in memory caching, interactive response times cannot be achieved for all datasets (note that it is common to analyze data with 50 billion records in PowerDrill). In this paper, we investigate two orthogonal approaches to optimize performance at the expense of an acceptable loss of accuracy. Both approaches can be implemented as outer wrappers around existing database engines and so they should be easily applicable to other systems. For the first optimization we show that memory is the limiting factor in executing queries at speed and therefore explore possibilities to improve memory efficiency. We adapt some of the theory behind data sketches to reduce the size of particularly expensive fields in our largest tables by a factor of 4.5 when compared to a standard compression algorithm. This saves 37% of the overall memory in PowerDrill and introduces a 0.4% relative error in the 90th percentile for results of queries with the expensive fields. We additionally evaluate the effects of using sampling on accuracy and propose a simple heuristic for annotating individual result-values as accurate (or not). Based on measurements of user behavior in our real production system, we show that these estimates are essential for interpreting intermediate results before final results are available. For a large set of queries this effectively brings down the 95th latency percentile from 30 to 4 seconds.

Keywords: big data, in-memory column-store, high-performance SQL queries, approximate SQL queries

Procedia PDF Downloads 246

Authors: Masoud Soltani Hosseini, Fereshteh Rahmani, Mohammad Tajik Mansouri, Ali Zolghadr

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Climate change is accompanied with ambient temperature increase and water accessibility limitation. The main objective of this paper is to investigate the effects of climate change on thermal power plants including gas turbines, steam and combined cycle power plants in Iran. For this purpose, the ambient temperature increase and water accessibility will be analyzed and their effects on power output and efficiency of thermal power plants will be determined. According to the results, the ambient temperature has high effect on steam power plants with indirect cooling system (Heller). The efficiency of this type of power plants decreases by 0.55 percent per 1oC ambient temperature increase. This amount is 0.52 and 0.2 percent for once-through and wet cooling systems, respectively. The decrease in power output covers a range of 0.2% to 0.65% for steam power plant with wet cooling system and gas turbines per 1oC air temperature increase. Based on the thermal power plants distribution in Iran and different scenarios of climate change, the total amount of power output decrease falls between 413 and 1661 MW due to ambient temperature increase. Another limitation incurred by climate change is water accessibility. In optimistic scenario, the power output of steam plants decreases by 1450 MW in dry and hot climate areas throughout next decades. The remaining scenarios indicate that the amount of decrease in power output would be by 4152 MW in highlands and cold climate. Therefore, it is necessary to consider appropriate solutions to overcome these limitations. Considering all the climate change effects together, the actual power output falls in range of 2465 and 7294 MW and efficiency loss covers the range of 0.12 to .56 % in different scenarios.

Keywords: climate, change, thermal, power plants

Procedia PDF Downloads 64

Authors: Penina Orenstein

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In today’s world, particularly with COVID-19 a constant worldwide threat, organizations need greater visibility over their supply chains more than ever before, in order to find areas for improvement and greater efficiency, reduce the chances of disruption and stay competitive. The concept of supply chain mapping is one where every process and route is mapped in detail between each vendor and supplier. The simplest method of mapping involves sourcing publicly available data including news and financial information concerning relationships between suppliers. An additional layer of information would be disclosed by large, direct suppliers about their production and logistics sites. While this method has the advantage of not requiring any input from suppliers, it also doesn’t allow for much transparency beyond the first supplier tier and may generate irrelevant data—noise—that must be filtered out to find the actionable data. The primary goal of this research is to build data maps of supply chains by focusing on a layered approach. Using these maps, the secondary goal is to address the question as to whether the supply chain is re-engineered to make improvements, for example, to lower the carbon footprint. Using a drill-down approach, the end result is a comprehensive map detailing the linkages between tier-one, tier-two, and tier-three suppliers super-imposed on a geographical map. The driving force behind this idea is to be able to trace individual parts to the exact site where they’re manufactured. In this way, companies can ensure sustainability practices from the production of raw materials through the finished goods. The approach allows companies to identify and anticipate vulnerabilities in their supply chain. It unlocks predictive analytics capabilities and enables them to act proactively. The research is particularly compelling because it unites network science theory with empirical data and presents the results in a visual, intuitive manner.

Keywords: data mining, supply chain, empirical research, data mapping

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Authors: Güllü Yakar, Adnan Tepecik

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A university campus resembles an independent city that is spread over a wide area. Campuses that incorporate thousands of new domestic and international users at the beginning of every academic period also host scientific, cultural and sportive events, in addition to embodying regular users such as students and staff. Wayfinding and signage systems are necessary for the regulation of vehicular traffic, and they enable users’ to navigate without losing time or feeling anxiety. While designing the system or testing the functionality of it, opinions of existing users or likely behaviors of typical user profiles (personas) provide designers with insight. The purpose of this study is to identify the wayfinding attitudes and expectations of Kastamonu University Kuzeykent Campus users. This study applies a mixed method in which a questionnaire, developed by the researcher, constitute the quantitative phase of the study. The survey was carried out with 850 participants who filled a questionnaire form which was tested in terms of construct validity by using Exploratory Factor Analysis. While interpreting the data obtained, Chi-Square, T- Test and ANOVA analyses were applied as well as descriptive analyses such as frequency (f) and percentage (%) values. The results of this survey, which was conducted during the absence of systematic wayfinding signs in the campus, reveals the participants expectations for insertion of floor plans and wayfinding signs to indoors, maps to outdoors, symbols and color codes to the existing signs and for the adequate arrangement of those for the use of visually impaired people. The fact that there is a direct proportional relation between the length of institution membership and wayfinding competency within campus, leads to the conclusion that especially the new comers are in need of wayfinding signs. In order to determine the effectiveness of campus-wide wayfinding system implemented after the survey and in order to identify the further expectations of users in this respect, a semi-structured interview form developed by the researcher and assessments of 20 participants are compiled. Subjected to content analysis, this data constitute the qualitative dimension of the study. Research results indicate that despite the presence of the signs, the participants experienced either inability or stress while finding their way, showed tendency to receive help from others and needed outdoor maps and signs, in addition to bigger-sized texts.

Keywords: environmental graphic design, environmental perception, wayfinding and signage design, wayfinding system

Procedia PDF Downloads 218

Authors: Guanglin Song

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(Objective) Situated within the context of China's tiered medical treatment system, this study aims to analyze spatial causes of urban healthcare access difficulties from the perspective of the configuration of healthcare facilities. (Methods) A social network analysis approach is employed to construct a healthcare demand and supply flow network between major residential clusters and various tiers of hospitals in the city.(Conclusion) The findings reveal that:1.there exists overall maldistribution and over-concentration of healthcare resources in Study Area, characterized by structural imbalance; 2.the low rate of primary care utilization in Study Area is a key factor contributing to congestion at higher-tier hospitals, as excessive reliance on these institutions by neighboring communities exacerbates the problem; 3.gradual optimization of the healthcare facility layout in Study Area, encompassing holistic, local, and individual institutional levels, can enhance systemic efficiency and resource balance.(Prospects) This research proposes a method for evaluating urban healthcare resource distribution structures based on service flows within hierarchical networks. It offers spatially targeted optimization suggestions for promoting the implementation of the tiered healthcare system and alleviating challenges related to accessibility and congestion in seeking medical care. Provide some new ideas for researchers and healthcare managers in countries, cities, and healthcare management around the world with similar challenges.

Keywords: flow of public services, urban networks, healthcare facilities, spatial planning, urban networks

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Authors: Julian Iliev

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The recent release of The Matrix Resurrections persuaded many film scholars that The Matrix trilogy had lost its appeal and its concepts were largely outdated. This study examines the human pods and growing fields in the trilogy. Their functionality is compared to Michel Foucault’s concept of docile bodies: linking fictional and contemporary worlds. This paradigm is scrutinized through surveillance literature. The analogy brings to light common elements of hidden surveillance practices in technologies. The comparison illustrates the effects of body manipulation portrayed in the movies and their relevance with contemporary surveillance practices. Many scholars have utilized a close reading methodology in film studies (J.Bizzocchi, J.Tanenbaum, P.Larsen, S. Herbrechter, and Deacon et al.). The use of a particular lens through which media text is examined is an indispensable factor that needs to be incorporated into the methodology. The study spotlights both scenes from the trilogy depicting the human pods and growing fields. The functionality of the pods and the fields compare directly with Foucault’s concept of docile bodies. By utilizing Foucault’s study as a lens, the research will unearth hidden components and insights into the films. Foucault recognizes three disciplines that produce docile bodies: 1) manipulation and the interchangeability of individual bodies, 2) elimination of unnecessary movements and management of time, and 3) command system guaranteeing constant supervision and continuity protection. These disciplines can be found in the pods and growing fields. Each body occupies a single pod aiding easier manipulation and fast interchangeability. The movement of the bodies in the pods is reduced to the absolute minimum. Thus, the body is transformed into the ultimate object of control – minimum movement correlates to maximum energy generation. Supervision is exercised by wiring the body with numerous types of cables. This ultimate supervision of body activity reduces the body’s purpose to mere functioning. If a body does not function as an energy source, then it’s unplugged, ejected, and liquefied. The command system secures the constant supervision and continuity of the process. To Foucault, the disciplines are distinctly different from slavery because they stop short of a total takeover of the bodies. This is a clear difference from the slave system implemented in the films. Even though their system might lack sophistication, it makes up for it in the elevation of functionality. Further, surveillance literature illustrates the connection between the generation of body energy in The Matrix trilogy to the generation of individual data in contemporary society. This study found that the three disciplines producing docile bodies were present in the portrayal of the pods and fields in The Matrix trilogy. The above comparison combined with surveillance literature yields insights into analogous processes and contemporary surveillance practices. Thus, the constant generation of energy in The Matrix trilogy can be equated to the consistent data generation in contemporary society. This essay shows the relevance of the body manipulation concept in the Matrix films with contemporary surveillance practices.

Keywords: docile bodies, film trilogies, matrix movies, michel foucault, privacy loss, surveillance

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Authors: Shokouh Momeni, Mohammad Reza Salamat, Ali Asghar Rastegari

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Background: Osteoporosis is the most prevalent metabolic bone disease in postmenopausal women associated with reduced bone mass and increased bone fracture. Measuring bone density in the lumbar spine and hip is a reliable measure of bone mass and can therefore specify the risk of fracture. Dual-energy X-ray absorptiometry(DXA) is an accurate non-invasive system measuring the bone density, with low margin of error and no complications. The present study aimed to investigate the relationship between biochemical parameters with bone density in postmenopausal women. Materials and methods: This cross-sectional study was conducted on 87 postmenopausal women referred to osteoporosis centers in Isfahan. Bone density was measured in the spine and hip area using DXA system. Serum levels of calcium, phosphorus, alkaline phosphatase and magnesium were measured by autoanalyzer and serum levels of vitamin D were measured by high-performance liquid chromatography(HPLC). Results: The mean parameters of calcium, phosphorus, alkaline phosphatase, vitamin D and magnesium did not show a significant difference between the two groups(P-value>0.05). In the control group, the relationship between alkaline phosphatase and BMC and BA in the spine was significant with a correlation coefficient of -0.402 and 0.258, respectively(P-value<0.05) and BMD and T-score in the femoral neck area showed a direct and significant relationship with phosphorus(Correlation=0.368; P-value=0.038). There was a significant relationship between the Z-score with calcium(Correlation=0.358; P-value=0.044). Conclusion: There was no significant relationship between the values ​​of calcium, phosphorus, alkaline phosphatase, vitamin D and magnesium parameters and bone density (spine and hip) in postmenopaus

Keywords: osteoporosis, menopause, bone mineral density, vitamin d, calcium, magnesium, alkaline phosphatase, phosphorus

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Authors: James Boylan, Denny Meyer, Won Sun Chen

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Background: Globally, there is an increasing trend of road traffic deaths, reaching 1.35 million in 2016 in comparison to 1.3 million a decade ago, and overall, road traffic injuries are ranked as the eighth leading cause of death for all age groups. The reported death rate for younger drivers aged 16-19 years is almost twice the rate reported for older drivers aged 25 and above, with a rate of 3.5 road traffic fatalities per annum for every 10,000 licenses held. Telematics refers to a system with the ability to capture real-time data about vehicle usage. The data collected from telematics can be used to better assess a driver's risk. It is typically used to measure acceleration, turn, braking, and speed, as well as to provide locational information. With the Australian government creating the National Telematics Framework, there has been an increase in the government's focus on using telematics data to improve road safety outcomes. The purpose of this study is to test the hypothesis that improvements in telematics measured driving behaviour to relate to improvements in road safety attitudes measured by the Driving Behaviour Questionnaire (DBQ). Methodology: 28 participants were recruited and given a telematics device to insert into their vehicles for the duration of the study. The participant's driving behaviour over the course of the first month will be compared to their driving behaviour in the second month to determine whether feedback from telematics devices improves driving behaviour. Participants completed the DBQ, evaluated using a 6-point Likert scale (0 = never, 5 = nearly all the time) at the beginning, after the first month, and after the second month of the study. This is a well-established instrument used worldwide. Trends in the telematics data will be captured and correlated with the changes in the DBQ using regression models in SAS. Results: The DBQ has provided a reliable measure (alpha = .823) of driving behaviour based on a sample of 23 participants, with an average of 50.5 and a standard deviation of 11.36, and a range of 29 to 76, with higher scores, indicating worse driving behaviours. This initial sample is well stratified in terms of gender and age (range 19-27). It is expected that in the next six weeks, a larger sample of around 40 will have completed the DBQ after experiencing in-vehicle telematics for 30 days, allowing a comparison with baseline levels. The trends in the telematics data over the first 30 days will be compared with the changes observed in the DBQ. Conclusions: It is expected that there will be a significant relationship between the improvements in the DBQ and the trends in reduced telematics measured aggressive driving behaviours supporting the hypothesis.

Keywords: telematics, driving behavior, young drivers, driving behaviour questionnaire

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Authors: Tomoya Oshiro, Hiroko Ono

Abstract:

Japan's aging population is increasing due to the decrease in birthrate. It causes various problems like the decrease in the gross domestic product of the country. The reason is why the local government of Japan has been on the way to a sustainable city recently. Then it is essential to get control of an urban structure to make the compact city successful. There are many kinds of paper about the compact city; however, the paper about a compact city of the island-type city is less. The purpose of this study is to clarify difference of urban structure between an island-type and a general city type. The method which has conducted in this research has two steps. First of all, by using evaluation indexes in the handbook, we evaluated the urban structures among each same -population-class cities from 50,000 to 100,000 people. Next, to clear the difference about the urban structure and feature between island-type and general-type cities compare the radar chart which is composed with each evaluation indexes of urban structure. Moreover, in order to clarify the relationship between evaluation indexes and the place of residence by using GIS software to show up population density on the map. As a result of this research, the management of local government and the local economy in evaluation indexes are indicated to be negative point in comparison of island-type cities with general cities. However, evaluation indexes of safety/security and low-carbon/energy are proved to be positive point. The research to find the difference features of the island-type of urban structure proves that the management of local government or the local economy is negative point in these island-type cities. In addition, the public transportation coverage in Miyako Island, Sado Island, and Amakusa Island show low value compare with other islands and average value. Relationship between evaluation indexes of an urban structure and the place of residence prove that the place of residence is related to public transportation coverage. If the place of residence is spread out, the public transportation coverage will be decreased. The results of this research reveal that the finances in island-type cities are negative point compare to general cities. This problem is caused by declining population. In addition, the place of residence is related to the public transportation coverage. Even though, it needs a much money to increase the public transportation coverage. It is possibly to cause other problems furthermore the aspect of finance is influenced by that as well. The conclusion in this research suggests that it is important for creating the compact city in island-type cities that we first need to address solving the problems about the management of local government and the local economy.

Keywords: sustainable city, comparative analysis, geographic information system, urban structure

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Authors: Shrikant Charhate, Gayatri Deshpande

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Permeable pavements have significant benefits like managing runoff, infiltration, and carrying traffic over conventional pavements in terms of sustainability and environmental impact. Some of the countries are using this technique, especially at locations where durability and other parameters are of importance in nature; however, sparse work has been done on this concept. In India, this is yet to be adopted. In this work, the progress in the characterization and development of Permeable Articulated Concrete Blocks (PACB) pavement design is described and discussed with reference to Indian conditions. The experimentation and in-depth analysis was carried out considering conditions like soil erosion, water logging, and dust which are significant challenges caused due to impermeability of pavement. Concrete blocks with size 16.5’’x 6.5’’x 7’’ consisting of arch shape (4’’) at beneath and ½” PVC holes for articulation were casted. These blocks were tested for flexural strength. The articulation process was done with nylon ropes forming series of concrete block system. The total spacing between the blocks was kept about 8 to 10% of total area. The hydraulic testing was carried out by placing the articulated blocks with the combination of layers of soil, geotextile, clean angular aggregate. This was done to see the percentage of seepage through the entire system. The experimental results showed that with the shape of concrete block the flexural strength achieved was beyond the permissible limit. Such blocks with the combination could be very useful innovation in Indian conditions and useful at various locations compared to the traditional blocks as an alternative for long term sustainability.

Keywords: connections, geotextile, permeable ACB, pavements, stone base

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Authors: Ceren Karaman, Onur Karaman

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The adsorption of Remazol Black B (RBB), an anionic dye, onto dried orange pulp (DOP) adsorbent prepared by only drying and by treating with cetyltrimetylammonium bromide (CTAB), a cationic surfactant, surface-modified orange pulp (SMOP) was studied in a stirred batch experiments system at 25°C. The adsorption of RBB on each adsorbent as a function of surfactant dosage, initial pH of the solution and initial dye concentration was investigated. The optimum amount of CTAB was found to be 25g/l. For RBB adsorption studies, while working pH value for the DOP adsorbent system was determined as 2.0, it was observed that this value shifted to 8.0 when the 25 g/l CTAB treated-orange pulp (SMOP) adsorbent was used. It was obtained that the adsorption rate and capacity increased to a certain value, and the adsorption efficiency decreased with increasing initial RBB concentration for both DOP and SMOP adsorbents at pH 2.0 and pH 8.0. While the highest adsorption capacity for DOP was determined as 62.4 mg/g at pH 2.0, and as 325.0 mg/g for SMOP at pH 8.0. As a result, it can be said that permanent cationic coating of the adsorbent surface by CTAB surfactant shifted the working pH from 2.0 to 8.0 and it increased the dye adsorption rate and capacity of orange pulp much more significantly at pH 8.0. The equilibrium RBB adsorption data on each adsorbent were best described by the Langmuir isotherm model. The adsorption kinetics of RBB on each adsorbent followed a pseudo-second-order model. Moreover, the intraparticle diffusion model was used to describe the kinetic data. It was found that diffusion is not the only rate controlling step. The adsorbent was characterized by the Brunauer–Emmett–Teller (BET) analysis, Fourier-transform-infrared (FTIR) spectroscopy, and scanning-electron-microscopy (SEM). The mechanism for the adsorption of RBB on the SMOP may include hydrophobic interaction, van der Waals interaction, stacking and electrostatic interaction.

Keywords: adsorption, Cetyltrimethylammonium Bromide (CTAB), orange pulp, Remazol Black B (RBB), surface modification

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Authors: Rutebuka Evariste, Zhang Lixiao

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Mobile phone sales and stocks showed an exponential growth in the past years globally and the number of mobile phones produced each year was surpassing one billion in 2007, this soaring growth of related e-waste deserves sufficient attentions paid to it regionally and globally as long as 40% of its total weight is made from metallic which 12 elements are identified to be highly hazardous and 12 are less harmful. Different research and methods have been used to estimate the obsolete mobile phones but none has developed a dynamic model and handle the discrepancy resulting from improper approach and error in the input data. The study aim was to develop a comprehensive dynamic system model for simulating the dynamism of e-waste production from mobile phone regardless the country or region and prevail over the previous errors. The logistic model method combined with STELLA program has been used to carry out this study. Then the simulation for Rwanda has been conducted and compared with others countries’ results as model testing and validation. Rwanda is about 1.5 million obsoletes mobile phone with 125 tons of waste in 2014 with e-waste production peak in 2017. It is expected to be 4.17 million obsoletes with 351.97 tons by 2020 along with environmental impact intensity of 21times to 2005. Thus, it is concluded through the model testing and validation that the present dynamic model is competent and able deal with mobile phone e-waste production the fact that it has responded to the previous studies questions from Czech Republic, Iran, and China.

Keywords: carrying capacity, dematerialization, logistic model, mobile phone, obsolescence, similarity, Stella, system dynamics

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Authors: Md Imtiaz, Sanchita Dei, Shubham Damke

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In recent years, there has been a rapidly accelerating shift from traditional surface processing operations to subsea processing operation. This shift has been driven by a number of factors including the depletion of shallow fields around the world, technological advances in subsea processing equipment, the need for production from marginal fields, and lower initial upfront investment costs compared to traditional production facilities. Moving production facilities to the seafloor offers a number of advantage, including a reduction in field development costs, increased production rates from subsea wells, reduction in the need for chemical injection, minimization of risks to worker ,reduction in spills due to hurricane damage, and increased in oil production by enabling production from marginal fields. Subsea processing consists of a range of technologies for separation, pumping, compression that enables production from offshore well without the need for surface facilities. At present, there are two primary technologies being used for subsea processing: subsea multiphase pumping and subsea separation. Multiphase pumping is the most basic subsea processing technology. Multiphase pumping involves the use of boosting system to transport the multiphase mixture through pipelines to floating production vessels. The separation system is combined with single phase pumps or water would be removed and either pumped to the surface, re-injected, or discharged to the sea. Subsea processing can allow for an entire topside facility to be decommissioned and the processed fluids to be tied back to a new, more distant, host. This type of application reduces costs and increased both overall facility and integrity and recoverable reserve. In future, full subsea processing could be possible, thereby eliminating the need for surface facilities.

Keywords: FPSO, marginal field, Subsea processing, SWAG

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Authors: Shutchapol Chopvitayakun

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Nowadays, especially for the last 5 years, mobile devices, mobile applications and mobile users, through the deployment of wireless communication and mobile phone cellular network, all these components are growing significantly bigger and stronger. They are being integrated into each other to create multiple purposes and pervasive deployments into every business and non-business sector such as education, medicine, traveling, finance, real estate and many more. Objective of this study was to develop a mobile application for seniors or last-year students who enroll the internship program at each tertiary school (undergraduate school) and do onsite practice at real field sties, real organizations and real workspaces. During the internship session, all students as the interns are required to exercise, drilling and training onsite with specific locations and specific tasks or may be some assignments from their supervisor. Their work spaces are both private and government corporates and enterprises. This mobile application is developed under schema of a transactional processing system that enables users to keep daily work or practice log, monitor true working locations and ability to follow daily tasks of each trainee. Moreover, it provides useful guidance from each intern’s advisor, in case of emergency. Finally, it can summarize all transactional data then calculate each internship cumulated hours from the field practice session for each individual intern.

Keywords: internship, mobile application, Android OS, smart phone devices, mobile transactional processing system, guidance and monitoring, tertiary education, senior students, model view controller (MVC)

Procedia PDF Downloads 300

Authors: Ke-Jing Lee, Cheng-Jung Lee, Yu-Chi Chang, Li-Wen Wang, Yeong-Her Wang

Abstract:

To avoid the cross-talk issue of only resistive random access memory (RRAM) cell, one transistor and one resistor (1T1R) architecture with a TiO₂-based RRAM cell connected with solution barium zirconate nickelate (BZN) organic thin film transistor (OTFT) device is successfully demonstrated. The OTFT were fabricated on a glass substrate. Aluminum (Al) as the gate electrode was deposited via a radio-frequency (RF) magnetron sputtering system. The barium acetate, zirconium n-propoxide, and nickel II acetylacetone were synthesized by using the sol-gel method. After the BZN solution was completely prepared using the sol-gel process, it was spin-coated onto the Al/glass substrate as the gate dielectric. The BZN layer was baked at 100 °C for 10 minutes under ambient air conditions. The pentacene thin film was thermally evaporated on the BZN layer at a deposition rate of 0.08 to 0.15 nm/s. Finally, gold (Au) electrode was deposited using an RF magnetron sputtering system and defined through shadow masks as both the source and drain. The channel length and width of the transistors were 150 and 1500 μm, respectively. As for the manufacture of 1T1R configuration, the RRAM device was fabricated directly on drain electrodes of TFT device. A simple metal/insulator/metal structure, which consisting of Al/TiO₂/Au structures, was fabricated. First, Au was deposited to be a bottom electrode of RRAM device by RF magnetron sputtering system. Then, the TiO₂ layer was deposited on Au electrode by sputtering. Finally, Al was deposited as the top electrode. The electrical performance of the BZN OTFT was studied, showing superior transfer characteristics with the low threshold voltage of −1.1 V, good saturation mobility of 5 cm²/V s, and low subthreshold swing of 400 mV/decade. The integration of the BZN OTFT and TiO₂ RRAM devices was finally completed to form 1T1R configuration with low power consumption of 1.3 μW, the low operation current of 0.5 μA, and reliable data retention. Based on the I-V characteristics, the different polarities of bipolar switching are found to be determined by the compliance current with the different distribution of the internal oxygen vacancies used in the RRAM and 1T1R devices. Also, this phenomenon can be well explained by the proposed mechanism model. It is promising to make the 1T1R possible for practical applications of low-power active matrix flat-panel displays.

Keywords: one transistor and one resistor (1T1R), organic thin-film transistor (OTFT), resistive random access memory (RRAM), sol-gel

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Authors: Hamidreza Hoshyarmanesh, Hosein Madieh, Sanju Lama, Yaser Maddahi, Garnette R. Sutherland, Kourosh Zareinia

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This paper illustrates the concept of an algorithm to register specified markers on the neuroArm surgical manipulators, an image-guided MR-compatible tele-operated robot for microsurgery and stereotaxy. Two range-finding algorithms, namely time-of-flight and phase-shift, are evaluated for registration and supervisory control. The time-of-flight approach is implemented in a semi-field experiment to determine the precise position of a tiny retro-reflective moving object. The moving object simulates a surgical tool tip. The tool is a target that would be connected to the neuroArm end-effector during surgery inside the magnet bore of the MR imaging system. In order to apply flight approach, a 905-nm pulsed laser diode and an avalanche photodiode are utilized as the transmitter and receiver, respectively. For the experiment, a high frequency time to digital converter was designed using a field-programmable gate arrays. In the phase-shift approach, a continuous green laser beam with a wavelength of 530 nm was used as the transmitter. Results showed that a positioning error of 0.1 mm occurred when the scanner-target point distance was set in the range of 2.5 to 3 meters. The effectiveness of this non-contact approach exhibited that the method could be employed as an alternative for conventional mechanical registration arm. Furthermore, the approach is not limited by physical contact and extension of joint angles.

Keywords: 3D laser scanner, intraoperative MR imaging, neuroArm, real time registration, robot-assisted surgery, supervisory control

Procedia PDF Downloads 274

Authors: Amira Benabdelkader

Abstract:

Communication presents the channel by which humankind create and maintain their relationship with others, express themselves, exchange information, learn and teach etc. The context of communication plays a distinctive role in deciding about the language to be used. The term context is mainly used to refer to the interlocutors, their cultures, languages, relationship, physical surrounding that is the communication setting, type of the information to be transmitted, the topic etc. Cultures, on one hand, impose on humans certain behaviours, attitudes, gestures and beliefs. On the other hand, the focus on language is inevitable as it is with its verbal and non-verbal components, a key tool in and for communication. Moreover, each language has its particularity in how people voice, address and express their thoughts, feelings and beliefs. Being in the same setting with people from different cultures and languages and having conversations with them would call upon the intercultural communicative competence. This latter would promote the success of their conversations. Additionally, this competence could manifest in several ways during their interactions, to the extent that no one can predict when and how the interlocutors would use it. The only thing probably that could be confirmed is that the setting and culture would in a way or another intervene and often shape the flow of their communication, if not the whole communication. Therefore, this paper will look at the intercultural communicative competence of language learners when introducing their cultures to each other in an online language tandem (henceforth OLT) using their second and/or foreign language with the L1 language speakers. The participants of this study are Algerian (use L2: French, FL: English), British (L1: English, L2/FL: French). In other words, this current paper will provide a qualitative analysis of the OLT experiment by emphasising how language learners can overcome the cultural differences in an intercultural setting while communicating online using Skype (video conversations) with people from different countries, cultures and L1. The non-verbal cues will have the lion share in the analysis by focusing on how they have been used to maintain this intercultural communication or hinder it through the misinterpretation of gestures, head movements, grimaces etc.

Keywords: intercultural communicative competence, non-verbal cues, online language tandem, Skype

Procedia PDF Downloads 263

Authors: Mourad Bédir, Sami Khomsi, Hakim Gabtni, Hajer Azaiez, Ramzi Gharsalli, Riadh Chebbi

Abstract:

Eastern Tunisia is a semi-arid area; located in the northern Africa plate; southern Mediterranean side. It is facing water scarcity, overexploitation, and decreasing of water quality of phreatic water table. Water supply and storage will not respond to the demographic and economic growth and demand. In addition, only 5 109 m3 of rainwater from 35 109 m3 per year renewable rain water supply can be retained and remobilized. To remediate this water deficiency, researches had been focused to near new subsurface deep aquifers resources. Among them, Upper Miocene sandstone deposits of Béglia, Saouaf, and Somaa Formations. These sandstones are known for their proven Hydrogeologic and hydrocarbon reservoir characteristics in the Tunisian margin. They represent semi-confined to confined aquifers. This work is based on new integrated approaches of seismic stratigraphy, seismic tectonics, and hydrogeology, to highlight and characterize these reservoirs levels for aquifer exploitation in semi-arid area. As a result, five to six third order sequence deposits had been highlighted. They are composed of multi-layered extended sandstones reservoirs; separated by shales packages. These reservoir deposits represent lowstand and highstand system tracts of these sequences, which represent lowstand and highstand system tracts of these sequences. They constitute important strategic water resources volumes for the region.

Keywords: Tunisia, Hydrogeology, sandstones, basin, seismic, aquifers, modeling

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Authors: Kyu Bum Han, Eunjin Jeon, Kimberly Watts, Brenda Payan Medina

Abstract:

Gen3 Concentrating Solar Power (CSP) high-temperature thermal systems have the potential to lower the cost of a CSP system. When compared to the other systems (chloride salt blends and supercritical fluids), the particle transport system can avoid many of the issues associated with high fluid temperature systems at high temperature because of its ability to operate at ambient pressure with limited corrosion or thermal stability risk. Furthermore, identifying and demonstrating low-cost particles that have excellent optical properties and durability can significantly reduce the levelized cost of electricity (LCOE) of particle receivers. The currently available thermal transfer particle in the study and market is oxidized at about 700oC, which reduces its durability, generates particle loss by high friction loads, and causes the color change. To meet the CSP SunShot goal, the durability of particles must be improved by identifying particles that are less abrasive to other structural materials. Furthermore, the particles must be economically affordable and the solar absorptance of the particles must be increased while minimizing thermal emittance. We are studying a novel thermal transfer particle, which has low cost, high durability, and high solar absorptance at high temperatures. The particle minimizes thermal emittance and will be less abrasive to other structural materials. Additionally, the particle demonstrates reusability, which significantly lowers the LCOE. This study will contribute to two principal disciplines of energy science: materials synthesis and manufacturing. Developing this particle for thermal transfer will have a positive impact on the ceramic study and industry as well as the society.

Keywords: concentrating solar power, thermal energy storage, particle, reusability, economics

Procedia PDF Downloads 212

Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

Procedia PDF Downloads 114