Search results for: deep graphical model

Authors: Ananya Govindarajan

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Tetrahymena thermophila is a single-cell, eukaryotic organism that belongs to the Protozoa Kingdom. Tetrahymena thermophila is often used in signal transduction pathway studies because of its ability to model sensory input and the effects of environmental conditions such as chemicals and temperature. The recently discovered G37 chemorepellent receptor showed increased responsiveness to all chemorepellents. Investigating the mutant G37 Tetrahymena gene in various test solutions, including ferric chloride, ferrous sulfate, hydrogen peroxide, tetrazolium blue, potassium chloride, and dithiothreitol were performed to determine the role of oxidants and reducing agents with the mutant and wild-type cells (CU427) to assess the role of the receptor. Behavioral assays and recordings processed by ImageJ indicated that ferric chloride, hydrogen peroxide, and tetrazolium blue yielded little to no chemorepellent responses from G37 cells (<20% ARs). CU427 cells were over-responsive based on the mean percent of cells (>50% ARs). Reducing agents elicited chemorepellent responses from both G37 and CU427, in addition to potassium chloride. Cell responses were classified as over-responsive (>50% ARs). Dithiothreitol yielded unexpected results as G37 (37.0% ARs) and CU427 (38.1% ARs) had relatively similar responses and were only responsive and not over-responsive to the reducing agent test chemical solution. Ultimately, this indicates that the G37 receptor is more interactive with molecules that are reducing agents or non-oxidant compounds; G37 may be unable to sense and respond to oxidants effectively, further elucidating the pathways of the G37 strain and nature of this receptor. Results also indicate that the CSF most likely contained an oxidant, like ferric chloride. This research can be further applied to neuronal influences and how specific compounds may affect human neurons individually and their excitability as the responses model action potentials and membrane potential.

Keywords: tetrahymena thermophila, signal transduction, chemosensory, oxidant, reducing agent

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Authors: Filomena Lopes, Miguel Magalhaes, Carla Santos Pereira, Natercia Durao, Cristina Costa-Lobo

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The option to implement curricular internships with undergraduate students is a pedagogical option with some good results perceived by academic staff, employers, and among graduates in general and IT (Information Technology) in particular. Knowing that this type of exercise has never been so relevant, as one tries to give meaning to the future in a landscape of rapid and deep changes. We have as an example the potential disruptive impact on the jobs of advances in robotics, artificial intelligence and 3-D printing, which is a focus of fierce debate. It is in this context that more and more students and employers engage in the pursuit of career-promoting responses and business development, making their investment decisions of training and hiring. Three decades of experience and research in computer science degree and in information systems technologies degree at the Portucalense University, Portuguese private university, has provided strong evidence of its advantages. The Human Interaction Skills development as well as the attractiveness of such experiences for students are topics assumed as core in the Ccnception and management of the activities implemented in these study cycles. The objective of this paper is to gather evidence of the Human Interaction Skills explained and valued within the curriculum internship experiences of IT students employability. Data collection was based on the application of questionnaire to intern counselors and to students who have completed internships in these undergraduate courses in the last decade. The trainee supervisor, responsible for monitoring the performance of IT students in the evolution of traineeship activities, evaluates the following Human Interaction Skills: Motivation and interest in the activities developed, interpersonal relationship, cooperation in company activities, assiduity, ease of knowledge apprehension, Compliance with norms, insertion in the work environment, productivity, initiative, ability to take responsibility, creativity in proposing solutions, and self-confidence. The results show that these undergraduate courses promote the development of Human Interaction Skills and that these students, once they finish their degree, are able to initiate remunerated work functions, mainly by invitation of the institutions in which they perform curricular internships. Findings obtained from the present study contribute to widen the analysis of its effectiveness in terms of future research and actions in regard to the transition from Higher Education pathways to the Labour Market.

Keywords: human interaction skills, employability, internships, information technology, higher education

Procedia PDF Downloads 276

Authors: Luís Rocha, Adam Gąska, Enrico Savio, Michael Marxer, Christoph Battaglia

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The changes observed in the last years in the field of manufacturing and production engineering, popularly known as "Fourth Industry Revolution", utilizes the achievements in the different areas of computer sciences, introducing new solutions at almost every stage of the production process, just to mention such concepts as mass customization, cloud computing, knowledge-based engineering, virtual reality, rapid prototyping, or virtual models of measuring systems. To effectively speed up the production process and make it more flexible, it is necessary to tighten the bonds connecting individual stages of the production process and to raise the awareness and knowledge of employees of individual sectors about the nature and specificity of work in other stages. It is important to discover and develop a suitable education method adapted to the specificities of each stage of the production process, becoming an extremely crucial issue to exploit the potential of the fourth industrial revolution properly. Because of it, the project “Train4Dim” (T4D) intends to develop complex training material for digital manufacturing, including content for design, manufacturing, and quality control, with a focus on coordinate metrology and portable measuring systems. In this paper, the authors present an approach to using an active learning methodology for digital manufacturing. T4D main objective is to develop a multi-degree (apprenticeship up to master’s degree studies) and educational approach that can be adapted to different teaching levels. It’s also described the process of creating the underneath methodology. The paper will share the steps to achieve the aims of the project (training model for digital manufacturing): 1) surveying the stakeholders, 2) Defining the learning aims, 3) producing all contents and curriculum, 4) training for tutors, and 5) Pilot courses test and improvements.

Keywords: learning, Industry 4.0, active learning, digital manufacturing

Procedia PDF Downloads 85

Authors: Sevdenur Onger, Ali Asram Sagiroglu

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Hyperpigmentation is a cosmetically unappealing skin problem caused by an overabundance of melanin in the skin. Its pathophysiology is caused by melanocytes being exposed to paracrine melanogenic stimuli, which can upregulate melanogenesis-related enzymes (such as tyrosinase) and cause melanosome formation. Tyrosinase is linked to the development of melanosomes biochemically, and it is the main target of hyperpigmentation treatment. therefore, decreasing tyrosinase activity to reduce melanosomes has become the main target of hyperpigmentation treatment. Niacinamide (NA) is a natural chemical found in a variety of plants that is used as a skin-whitening ingredient in cosmetic formulations. NA decreases melanogenesis in the skin by inhibiting melanosome transfer from melanocytes to covering keratinocytes. Furthermore, NA protects the skin from reactive oxygen species and acts as a main barrier with the skin, reducing moisture loss by increasing ceramide and fatty acid synthesis. However, it is very difficult for hydrophilic compounds such as NA to penetrate deep into the skin. Furthermore, because of the nicotinic acid in NA, it is an irritant. As a result, we've concentrated on strategies to increase NA skin permeability while avoiding its irritating impacts. Since nanotechnology can affect drug penetration behavior by controlling the release and increasing the period of permanence on the skin, it can be a useful technique in the development of whitening formulations. Liposomes have become increasingly popular in the cosmetics industry in recent years due to benefits such as their lack of toxicity, high penetration ability in living skin layers, ability to increase skin moisture by forming a thin layer on the skin surface, and suitability for large-scale production. Therefore, liposomes containing NA were developed for this study. Different formulations were prepared by varying the amount of phospholipid and cholesterol and examined in terms of particle sizes, polydispersity index (PDI) and pH values. The pH values of the produced formulations were determined to be suitable with the pH value of the skin. Particle sizes were determined to be smaller than 250 nm and the particles were found to be of homogeneous size in the formulation (pdi<0.30). Despite the important advantages of liposomal systems, they have low viscosity and stability for topical use. For these reasons, in this study, liposomal cream formulations have been prepared for easy topical application of liposomal systems. As a result, liposomal cream formulations containing NA have been successfully prepared and characterized. Following the in-vitro release and ex-vivo diffusion studies to be conducted in the continuation of the study, it is planned to test the formulation that gives the most appropriate result on the volunteers after obtaining the approval of the ethics committee.

Keywords: delivery systems, hyperpigmentation, liposome, niacinamide

Procedia PDF Downloads 101

Authors: S. Subramaniam, J. S. A. Rao, P. Ramdas, K. R. Selvaduray, N. M. Han, M. K. Kutty, A. K. Radhakrishnan

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Immune system is a complex system where the immune cells have the capability to respond against a wide range of immune challenges including cancer progression. However, in the event of cancer development, tumour cells trigger immunosuppressive environment via activation of myeloid-derived suppressor cells and T regulatory (Treg) cells. The Treg cells are subset of CD4+ T lymphocytes, known to have crucial roles in regulating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Dysregulation of these mechanisms could lead to cancer progression and immune suppression. Recently, there are many studies reporting on the effects of natural bioactive compounds on immune responses against cancer. It was known that tocotrienol-rich-fraction consisting 70% tocotrienols and 30% α-tocopherol is able to exhibit immunomodulatory as well as anti-cancer properties. Hence, this study was designed to evaluate the effects of gamma-tocotrienol (G-T3) supplementation on T-reg cells in a syngeneic mouse model of breast cancer. In this study, female BALB/c mice were divided into two groups and fed with either soy oil (vehicle) or gamma-tocotrienol (G-T3) for two weeks followed by inoculation with tumour cells. All the mice continued to receive the same supplementation until day 49. The results showed a significant reduction in tumour volume and weight in G-T3 fed mice compared to vehicle-fed mice. Lung and liver histology showed reduced evidence of metastasis in tumour-bearing G-T3 fed mice. Besides that, flow cytometry analysis revealed T-helper cell population was increased, and T-regulatory cell population was suppressed following G-T3 supplementation. Moreover, immunohistochemistry analysis showed that there was a marked decrease in the expression of FOXP3 in the G-T3 fed tumour bearing mice. In conclusion, the G-T3 supplementation showed good prognosis towards breast cancer by enhancing the immune response in tumour-bearing mice. Therefore, gamma-T3 can be used as immunotherapy agent for the treatment of breast cancer.

Keywords: breast cancer, gamma tocotrienol, immune suppression, supplement

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Authors: Novee Lor C. Leyso, Maylin C. Palatino

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Under-five malnutrition continues to persist in the Philippines, particularly in the island Province of Marinduque, with prevalence of some forms of malnutrition even worsening in recent years. Local spatial cluster detection provides a spatial perspective in understanding this phenomenon as key in analyzing patterns of geographic variation, identification of community-appropriate programs and interventions, and focused targeting on high-risk areas. Using data from a province-wide household-based census conducted in 2014–2016, this study aimed to determine and evaluate spatial clusters of under-five malnutrition, across the province and within each municipality at the individual level using household location. Malnutrition was defined as weight-for-age z-score that fall outside the 2 standard deviations from the median of the WHO reference population. The Kulldorff’s elliptical spatial scan statistic in binomial model was used to locate clusters with high-risk of malnutrition, while adjusting for age and membership to government conditional cash transfer program as proxy for socio-economic status. One large significant cluster of under-five malnutrition was found southwest of the province, in which living in these areas at least doubles the risk of malnutrition. Additionally, at least one significant cluster were identified within each municipality—mostly located along the coastal areas. All these indicate apparent geographical variations across and within municipalities in the province. There were also similarities and disparities in the patterns of risk of malnutrition in each cluster across municipalities, and even within municipality, suggesting underlying causes at work that warrants further investigation. Therefore, community-appropriate programs and interventions should be identified and should be focused on high-risk areas to maximize limited government resources. Further studies are also recommended to determine factors affecting variations in childhood malnutrition considering the evidence of spatial clustering found in this study.

Keywords: Binomial model, Kulldorff’s elliptical spatial scan statistic, Philippines, under-five malnutrition

Procedia PDF Downloads 129

Authors: Mehrangiz Rezaee, Zabih Charrahi

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In the last decade, with increasing tourism destinations and tourism growth, we are witnessing the widespread impacts of tourism on the economy, environment and society. Tourism and its related economy are now undergoing a transformation and as one of the key pillars of business economics, it plays a vital role in the world economy. Activities related to tourism and providing services appropriate to it in an area, like many economic sectors, require the necessary context on its origin. Given the importance of tourism industry and tourism potentials of Yazd province in Iran, it is necessary to use a proper procedure for prioritizing different areas for proper and efficient planning. One of the most important goals of planning is foresight and creating balanced development in different geographical areas. This process requires an accurate study of the areas and potential and actual talents, as well as evaluation and understanding of the relationship between the indicators affecting the development of the region. At the global and regional level, the development of tourist resorts and the proper distribution of tourism destinations are needed to counter environmental impacts and risks. The main objective of this study is the sustainable development of suitable tourism areas. Given that tourism activities in different territorial areas require operational zoning, this study deals with the evaluation of territorial tourism using concepts such as land use, fitness and sustainable development. It is essential to understand the structure of tourism development and the spatial development of tourism using land use patterns, spatial planning and sustainable development. Tourism spatial planning implements different approaches. However, the development of tourism as well as the spatial development of tourism is complex, since tourist activities can be carried out in different areas with different purposes. Multipurpose areas have great important for tourism because it determines the flow of tourism. Therefore, in this paper, by studying the development and determination of tourism suitability that is related to spatial development, it is possible to plan tourism spatial development by developing a model that describes the characteristics of tourism. The results of this research determine the suitability of multi-functional territorial tourism development in line with spatial planning of tourism.

Keywords: land use change, spatial planning, sustainability, territorial tourist, Yazd

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Authors: Yuan-Jye Tseng, Jia-Shu Li

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To design a product with the given product requirement and design objective, there can be alternative ways to propose the detailed design specifications of the product. In the design modeling stage, alternative design cases with detailed specifications can be modeled to fulfill the product requirement and design objective. Therefore, in the design evaluation stage, it is required to perform an evaluation of the alternative design cases for deciding the final design. The purpose of this research is to develop a product evaluation model for evaluating the alternative design cases by integrated evaluating the criteria of functional design, Kansei design, and design for supply chain. The criteria in the functional design group include primary function, expansion function, improved function, and new function. The criteria in the Kansei group include geometric shape, dimension, surface finish, and layout. The criteria in the design for supply chain group include material, manufacturing process, assembly, and supply chain operation. From the point of view of value and cost, the criteria in the functional design group and Kansei design group represent the design value of the product. The criteria in the design for supply chain group represent the supply chain and manufacturing cost of the product. It is required to evaluate the design value and the supply chain cost to determine the final design. For the purpose of evaluating the criteria in the three criteria groups, a fuzzy analytic network process (FANP) method is presented to evaluate a weighted index by calculating the total relational values among the three groups. A method using the technique for order preference by similarity to ideal solution (TOPSIS) is used to compare and rank the design alternative cases according to the weighted index using the total relational values of the criteria. The final decision of a design case can be determined by using the ordered ranking. For example, the design case with the top ranking can be selected as the final design case. Based on the criteria in the evaluation, the design objective can be achieved with a combined and weighted effect of the design value and manufacturing cost. An example product is demonstrated and illustrated in the presentation. It shows that the design evaluation model is useful for integrated evaluation of functional design, Kansei design, and design for supply chain to determine the best design case and achieve the design objective.

Keywords: design for supply chain, design evaluation, functional design, Kansei design, fuzzy analytic network process, technique for order preference by similarity to ideal solution

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Authors: Anuraj Singh

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The complex dynamics is explored in a prey predator system with multiple delays. The predator dynamics is governed by Leslie-Gower scheme. The existence of periodic solutions via Hopf bifurcation with respect to delay parameters is established. To substantiate analytical findings, numerical simulations are performed. The system shows rich dynamic behavior including chaos and limit cycles.

Keywords: chaos, Hopf bifurcation, stability, time delay

Procedia PDF Downloads 317

Authors: Zengda Li

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The tectonic evolution of the Beishan orogen, which forms part of the Central Asian Orogenic Belt, remains debated. This study reports the identification of three Triassic granitic plutons representing two distinct stages of magmatism in southern Beishan orogen. Zircon U–Pb dating constrains the early stage as 238–237 Ma and the late stage as 229–227 Ma. The granitoids belong to high-K calc-alkaline and shoshonitic series and exhibit alkalic-calcic and calc-alkalic features, and are weakly peraluminous rocks. Most of these granitoids are highly fractionated I-type and A-type granites. They have relatively high Isr values (0.7049–0.7086) and weak negative εNd(t) values of −1.5 to −2.1, with young Nd model ages of 1.04–0.91 Ga, indicating a crustal contribution. They also show markedly positive zircon εHf(t) values (+3.4 to +11.8) and two-stage Hf model ages of 1.06–0.69 Ga, indicating a mixture of mantle and crustal components. The lithospheric mantle beneath this region incorporating older subducted materials was metasomatized by fluids or melts. Partial melting of the metasomatized lithospheric mantle resulted in underplated magmas, which provided the heat and material input to generate the granitoids. The Middle Triassic granitic plutons show moderate negative Eu anomalies, enrichment of LILEs and depletion in Nb, Ta, and Ti suggesting partial melting of crustal components in response to the underplated mantle-derived magmas, probably linked to lithospheric delamination and asthenospheric upwelling. The Late Triassic granitic plutons show characteristics of post-orogenic granite with strong negative anomalies of Eu, Ba, Nb, Sr, P, and Ti, indicating fractional crystallization and crustal contamination during the emplacement process.

Keywords: Triassic, magmatism, geochronology, petrogenesis, Beishan orogen

Procedia PDF Downloads 144

Authors: Merouane Salhi, Mohamed Roudane, Abdelkader Kirad

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In this work, we present a new form of characteristics method, which is a technique for solving partial differential equations. Typically, it applies to first-order equations; the aim of this method is to reduce a partial differential equation to a family of ordinary differential equations along which the solution can be integrated from some initial data. This latter developed under the real gas theory, because when the thermal and the caloric imperfections of a gas increases, the specific heat and their ratio do not remain constant anymore and start to vary with the gas parameters. The gas doesn’t stay perfect. Its state equation change and it becomes for a real gas. The presented equations of the characteristics remain valid whatever area or field of study. Here we need have inserted the developed Prandtl Meyer function in the mathematical system to find a new model when the effect of stagnation pressure is taken into account. In this case, the effects of molecular size and intermolecular attraction forces intervene to correct the state equation, the thermodynamic parameters and the value of Prandtl Meyer function. However, with the assumptions that Berthelot’s state equation accounts for molecular size and intermolecular force effects, expressions are developed for analyzing the supersonic flow for thermally and calorically imperfect gas. The supersonic parameters depend directly on the stagnation parameters of the combustion chamber. The resolution has been made by the finite differences method using the corrector predictor algorithm. As results, the developed mathematical model used to design 2D minimum length nozzles under effect of the stagnation parameters of fluid flow. A comparison for air with the perfect gas PG and high temperature models on the one hand and our results by the real gas theory on the other of nozzles shapes and characteristics are made.

Keywords: numerical methods, nozzles design, real gas, stagnation parameters, supersonic expansion, the characteristics method

Procedia PDF Downloads 228

Authors: Aminah Abdullah, Iqbal Khadaroo

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This paper investigates to what ends, how and by whom museums and art galleries in the UK are governed, and to whom they provide accounts to justify their behavior and activities. A theoretical framework is developed by drawing from the governance and accountability literature and is fleshed out by using empirical data from secondary sources. The findings show that the governance model used, informed by the new public management (NPM) philosophy, and has created tensions between the managerial and social forms of accountability. Museums and art galleries have adopted a managerial culture of getting done what gets measured.

Keywords: governance, accountability, UK museums and art galleries, public sector

Procedia PDF Downloads 317

Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat

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We hypothesized that rexinoids such as bexarotene, a selective retinoid X receptor α (RXRα) agonist, may be beneficial for preventing mortality due to inflammation associated with increased expression/activity of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). Therefore, we investigated effects of bexarotene on the changes in circulating protein levels of iNOS (an index for systemic iNOS expression), myeloperoxidase (MPO) (an index for systemic inflammation), and lactate dehydrogenase (LDH) (an index for systemic tissue injury) in LPS-induced systemic inflammation model resulting in septic shock in rats. Rats were injected with saline (4 ml/kg; i.p.), LPS (10 mg/kg; i.p.), dimethylsulphoxide (4 ml/kg, 0.1%; s.c.) at time 0. Mean arterial blood pressure and heart rate were measured using a tail-cuff device. Bexarotene (0.03, 0.1, 0.3, and 1 mg/kg; s.c.) was administered to separate groups of rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and blood was collected for measurement of serum iNOS, MPO, and LDH protein levels. Blood pressure decreased by 31 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. Bexarotene at 0.3 and 1 mg/kg doses caused 20% mortality 4 h after LPS injection. In the LPS-treated rats, serum iNOS, MPO, and LDH protein levels were increased. Bexarotene only at 0.1 mg/kg dose prevented the LPS-induced hypotension and increased in iNOS, MPO, and LDH protein levels. These data are consistent with the view that a decrease in systemic iNOS levels contributes to the beneficial effect of bexarotene to prevent the hypotension associated with inflammation and tissue injury during rat endotoxemia. [This work was financially supported by The Scientific and Technological Research Council of Turkey (SBAG-109S121)].

Keywords: bexarotene, inflammation, iNOS, lipopolisaccharide, RXRa

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Authors: Yibeltal T. Bayou, Yohana S. Mashalla, Gloria Thupayagale-Tshweneagae

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Background: According to the World Health Organization, caesarean section delivery rates of more than 10-15% caesarean section deliveries in any specific geographic region in the world are not justifiable. The aim of the study was to describe the level and analyse determinants of caesarean section delivery in Addis Ababa. Methods: Data was collected in Addis Ababa using a structured questionnaire administered to 901 women aged 15-49 years through a stratified two-stage cluster sampling technique. Binary logistic regression model was employed to identify predictors of caesarean section delivery. Results: Among the 835 women who delivered their last birth at healthcare facilities, 19.2% of them gave birth by caesarean section. About 9.0% of the caesarean section births were due to mother’s request or service provider’s influence without any medical indication. The caesarean section delivery rate was much higher than the recommended rate particularly among the non-slum residents (27.2%); clients of private healthcare facilities (41.1%); currently married women (20.6%); women with secondary (22.2%) and tertiary (33.6%) level of education; and women belonging to the highest wealth quintile household (28.2%). The majority (65.8%) of the caesarean section clients were not informed about the consequences of caesarean section delivery by service providers. The logistic regression model shows that older age (30-49), secondary and above education, non-slum residence, high-risk pregnancy and receiving adequate antenatal care were significantly positively associated with caesarean section delivery. Conclusion: Despite the unreserved effort towards achieving MDG 5 through safe skilled delivery assistance among others, the high caesarean section rate beyond the recommend limit, and the finding that caesarean sections done without medical indications were also alarming. The government and city administration should take appropriate measures before the problems become setbacks in healthcare provision. Further investigations should focus on the effect of caesarean section delivery on maternal and child health outcomes in the study area.

Keywords: Addis Ababa, caesarean section, mode of delivery, slum residence

Procedia PDF Downloads 392

Authors: Nawt Almutairi, Ramzi El-Haddadeh

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With the extensive increase in the number of online shops, loyalty becomes the most purpose for e-retailers by which they can maintain their exit customers and regular income instead of spending large deal of money to target new segmentation. To obtain customers’ loyalty e-marketers should firstly satisfy customers by providing a high quality of services that could fulfil their demand. They have to satisfy them to trust the web-site then increase their intention to re-visit it. This study intends to investigate to what extend the elements of e-service quality presented in the literature affect customers’ satisfaction and how these influences contribute to customers’ trust and loyalty. Three dimensions of service quality are estimated. The first element is web-site interactivity, which is perceived the quality of interactive support and the accessible communications-tool. The second aspect is security/privacy, which is perceived the quality of controlling security and privacy while transaction over the web-site. The third element is web-design that perceived a pleasant user interface with visual appealing. These elements present positive effects on shoppers’ satisfaction. Thus, To examine the proposed constructs of this research, some measurements scale-items adapted from similar prior studies. Survey data collected online from Saudi customers (n=106) were utilized to test the research hypotheses. After that, the hypotheses were analyzed by using a variety of regression tools. The analytical results of this study propose that perceived quality of interactivity and security/privacy affects customers’ satisfaction. As well as trust seems to be a substantial construct that highly affects loyalty in online shopping. This study provides a developed model to obtain a simple understanding of the series of customers’ loyalty in online shopping. One construct presenting in the research model is web-design appears to be not important antecedent of satisfaction (the path to loyalty) in online shopping.

Keywords: e-service, satisfaction, trust, loyalty

Procedia PDF Downloads 243

Authors: B. Groß, P. Fronia, P. Nyhuis

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In addition to the production, which is already frequently optimized, improving the distribution logistics also opens up tremendous potential for increasing an enterprise’s competitiveness. Here too though, numerous interactions need to be taken into account, enterprises thus need to be able to identify and weigh between different potentials for economically efficient optimizations. In order to be able to assess potentials, enterprises require a suitable method. This paper first briefly presents the need for this research before introducing the procedure that will be used to develop an appropriate method that not only considers interactions but is also quickly and easily implemented.

Keywords: distribution logistics, evaluation of potential, methods, model

Procedia PDF Downloads 488

Authors: A. M. Byrne, E. Bonfiglio, C. Rigby, N. Edelstyn

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Introduction: Neuromarketing employs numerous methodologies when investigating products and advertisement effectiveness. Electroencephalography (EEG), a non-invasive measure of electrical activity from the brain, is commonly used in neuromarketing. EEG data can be considered using time-frequency (TF) analysis, where changes in the frequency of brainwaves are calculated to infer participant’s mental states, or event-related potential (ERP) analysis, where changes in amplitude are observed in direct response to a stimulus. This presentation discusses the findings of a systematic review of EEG measures in neuromarketing. A systematic review summarises evidence on a research question, using explicit measures to identify, select, and critically appraise relevant research papers. Thissystematic review identifies which EEG measures are the most robust predictor of customer preference and purchase intention. Methods: Search terms identified174 papers that used EEG in combination with marketing-related stimuli. Publications were excluded if they were written in a language other than English or were not published as journal articles (e.g., book chapters). The review investigated which TF effect (e.g., theta-band power) and ERP component (e.g., N400) most consistently reflected preference and purchase intention. Machine-learning prediction was also investigated, along with the use of EEG combined with physiological measures such as eye-tracking. Results: Frontal alpha asymmetry was the most reliable TF signal, where an increase in activity over the left side of the frontal lobe indexed a positive response to marketing stimuli, while an increase in activity over the right side indexed a negative response. The late positive potential, a positive amplitude increase around 600 ms after stimulus presentation, was the most reliable ERP component, reflecting the conscious emotional evaluation of marketing stimuli. However, each measure showed mixed results when related to preference and purchase behaviour. Predictive accuracy was greatly improved through machine-learning algorithms such as deep neural networks, especially when combined with eye-tracking or facial expression analyses. Discussion: This systematic review provides a novel catalogue of the most effective use of each EEG measure commonly used in neuromarketing. Exciting findings to emerge are the identification of the frontal alpha asymmetry and late positive potential as markers of preferential responses to marketing stimuli. Predictive accuracy using machine-learning algorithms achieved predictive accuracies as high as 97%, and future research should therefore focus on machine-learning prediction when using EEG measures in neuromarketing.

Keywords: EEG, ERP, neuromarketing, machine-learning, systematic review, time-frequency

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Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

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Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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Authors: Paola Molteni, Luigi d’Alonzo

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Background: Sensory issues are now considered one of the key aspects in defining and diagnosing autism, changing the perspectives on behavioural analysis and intervention in mainstream educational services. However, Italian teachers’ training is yet not specific on the topic of autism and its sensory-related effects and this research investigates the teacher’s capability in understanding the student’s needs and his/her challenging behaviours considering sensory perceptions. Objectives: The research aims to analyse mainstream schools teachers’ awareness on students’ sensory perceptions and how this affects classroom inclusion and learning process. The research questions are: i) Are teachers able to identify student’s sensory issues?; ii) Are trained teachers more able to identify sensory problems then untrained ones?; iii) What is the impact of sensory issues on inclusion in mainstream classrooms?; iv) What should teachers know about autistic sensory dimensions? Methods: This research was designed as a pilot study that involves a multi-methods approach, including action and collaborative research methodology. The designed research allows the researcher to catch the complexity of a province school district (from kindergarten to high school) through a deep detailed analysis of selected aspects. The researcher explored the questions described above through 133 questionnaires and 6 focus groups. The qualitative and quantitative data collected during the research were analysed using the Interpretative Phenomenological Analysis (IPA). Results: Mainstream schools teachers are not able to confidently recognise sensory issues of children included in the classroom. The research underlines: how professionals with no specific training on autism are not able to recognise sensory problems in students on the spectrum; how hearing and sight issues have higher impact on classroom inclusion and student’s learning process; how a lack of understanding is often followed by misinterpretations of the impact of sensory issues and challenging behaviours. Conclusions: As this research has shown, promoting and enhancing the importance of understanding sensory issues related to autism is fundamental to enable mainstream schools teachers to define educational and life-long plans able to properly answer the student’s needs and support his/her real inclusion in the classroom. This study is a good example of how the educational research can meet and help the daily practice in working with people on the autism spectrum and support the training design for mainstream school teachers: the emerging need of designed preparation on sensory issues is fundamental to be considered when planning school district in-service training programmes, specifically declined for inclusive services.

Keywords: autism spectrum condition, scholastic inclusion, sensory overload, teacher's training

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Authors: Nishantha Giguruwa

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This research investigates the transformative potential of smart container farming, building upon the successful cultivation of Japanese mushrooms at Sakai Farms in Aichi Prefecture, Japan, under the strategic collaboration with the Daikei Group. Inspired by this success, the study focuses on establishing an advanced urban strawberry farming laboratory with the aim of understanding strawberry farming technologies, fostering collaboration, and strategizing marketing approaches for both local and global markets. Positioned within the business framework of Sakai Farms and the Daikei Group, the study underscores the sustainability and forward-looking solutions offered by smart container farming in agriculture. The global significance of strawberries is emphasized, acknowledging their economic and cultural importance. The detailed examination of strawberry farming intricacies informs the technological framework developed for smart containers, implemented at Sakai Farms. Integral to this research is the incorporation of controlled bee pollination, a groundbreaking addition to the smart container farming model. The study anticipates future trends, outlining avenues for continuing exploration, stakeholder collaborations, policy considerations, and expansion strategies. Notably, the author expresses a strategic intent to approach the global market, leveraging the foreign student/faculty base at Ritsumeikan Asia Pacific University, where the author is affiliated. This unique approach aims to disseminate the research findings globally, contributing to the broader landscape of agricultural innovation. The integration of controlled bee pollination within this innovative framework not only enhances sustainability but also marks a significant stride in the evolution of urban agriculture, aligning with global agricultural trends.

Keywords: smart container farming, urban agriculture, strawberry farming technologies, controlled bee pollination, agricultural innovation

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Authors: Ebenezer O. Ige, Funmilayo H. Oyelami, Joshua Olutayo-Irheren, Joseph T. Okunlola

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Hyperthermia therapy is an adjuvant procedure during which perfused body tissues is subjected to elevated range of temperature in bid to achieve improved drug potency and efficacy of cancer treatment. While a selected class of hyperthermia techniques is shouldered on the thermal radiations derived from single-sourced electro-radiation measures, there are deliberations on conjugating dual radiation field sources in an attempt to improve the delivery of therapy procedure. This paper numerically explores the thermal effectiveness of combined infrared hyperemia having nanoparticle recirculation in the vicinity of imposed magnetic field on subcutaneous strata of a model lesion as ablation scheme. An elaborate Spectral relaxation method (SRM) was formulated to handle equation of coupled momentum and thermal equilibrium in the blood-perfused tissue domain of a spongy fibrous tissue. Thermal diffusion regimes in the presence of external magnetic field imposition were described leveraging on the renowned Roseland diffusion approximation to delineate the impact of radiative flux within the computational domain. The contribution of tissue sponginess was examined using mechanics of pore-scale porosity over a selected of clinical informed scenarios. Our observations showed for a substantial depth of spongy lesion, magnetic field architecture constitute the control regimes of hemodynamics in the blood-tissue interface while facilitating thermal transport across the depth of the model lesion. This parameter-indicator could be utilized to control the dispensing of hyperthermia treatment in intravenous perfused tissue.

Keywords: spectra relaxation scheme, thermal equilibrium, Roseland diffusion approximation, hyperthermia therapy

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Authors: Q. Giraud, J. Gonçalvès, B. Paris

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Remediation of dense non-aqueous phase liquids (DNAPLs) represents a challenging issue because of their persistent behaviour in the environment. This pilot-scale study investigates, by means of in situ experiments and numerical modelling, the feasibility of the pulsed pumping process of a large amount of a DNAPL in an alluvial aquifer. The main compound of the DNAPL is hexachlorobutadiene, an emerging organic pollutant. A low-permeability keyed enclosure was built at the location of the DNAPL source zone in order to isolate a finite undisturbed volume of soil, and a 3-month pulsed pumping process was applied inside the enclosure to exclusively extract the DNAPL. The water/DNAPL interface elevation at both the pumping and observation wells and the cumulated pumped volume of DNAPL were also recorded. A total volume of about 20m³ of purely DNAPL was recovered since no water was extracted during the process. The three-dimensional and multiphase flow simulator TMVOC was used, and a conceptual model was elaborated and generated with the pre/post-processing tool mView. Numerical model consisted of 10 layers of variable thickness and 5060 grid cells. Numerical simulations reproduce the pulsed pumping process and show an excellent match between simulated, and field data of DNAPL cumulated pumped volume and a reasonable agreement between modelled and observed data for the evolution of the water/DNAPL interface elevations at the two wells. This study offers a new perspective in remediation since DNAPL pumping system optimisation may be performed where a large amount of DNAPL is encountered.

Keywords: dense non-aqueous phase liquid (DNAPL), hexachlorobutadiene, in situ pulsed pumping, multiphase flow, numerical modelling, porous media

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Authors: Tae-Hoon Kim, Kwon-Ha Yoon, Hong Young Jun, Ki-Jong Kim, Young Hwan Lee, Myeung Su Lee, Keum Ha Choi, Ki Jung Yun, Eun Young Cho, Yong-Yeon Jeong, Chung-Hwan Jun

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Purpose: To assess the changes of hepatic metabolite for differentiation between non-alcoholic steatohepatitis (NASH) and simple steatosis on proton magnetic resonance spectroscopy (1H-MRS) in both humans and animal model. Methods: The local institutional review board approved this study and subjects gave written informed consent. 1H-MRS measurements were performed on a localized voxel of the liver using a point-resolved spectroscopy (PRESS) sequence and hepatic metabolites of alanine (Ala), lactate/triglyceride (Lac/TG), and TG were analyzed in NASH, simple steatosis and control groups. The group difference was tested with the ANOVA and Tukey’s post-hoc tests, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolic concentration and pathologic grades or non-alcoholic fatty liver disease(NAFLD) activity scores were assessed by the Pearson’s correlation. Results: Patient with NASH showed the elevated Ala(p<0.001), Lac/TG(p < 0.001), TG(p < 0.05) concentration when compared with patients who had simple steatosis and healthy controls. The NASH patients were higher levels in Ala(mean±SEM, 52.5±8.3 vs 2.0±0.9; p < 0.001), Lac/TG(824.0±168.2 vs 394.1±89.8; p < 0.05) than simple steatosis. The area under the ROC curve to distinguish NASH from simple steatosis was 1.00 (95% confidence interval; 1.00, 1.00) with Ala and 0.782 (95% confidence interval; 0.61, 0.96) with Lac/TG. The Ala and Lac/TG levels were well correlated with steatosis grade, lobular inflammation, and NAFLD activity scores. The metabolic changes in human were reproducible to a mice model induced by streptozotocin injection and a high-fat diet. Conclusion: 1H-MRS would be useful for differentiation of patients with NASH and simple hepatic steatosis.

Keywords: non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, 1H MR spectroscopy, hepatic metabolites

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Authors: Mabel Usunobun Olanipekun, Henry Ogbemudia Omoregbee

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Anomalies such as water pipeline and hydraulic or petrochemical pipeline network leakages and bursts have significant implications for economic conditions and the environment. In order to ensure pipeline systems are reliable, they must be efficiently controlled. Wireless Sensor Networks (WSNs) have become a powerful network with critical infrastructure monitoring systems for water, oil and gas pipelines. The loss of water, oil and gas is inevitable and is strongly linked to financial costs and environmental problems, and its avoidance often leads to saving of economic resources. Substantial repair costs and the loss of precious natural resources are part of the financial impact of leaking pipes. Pipeline systems experts have implemented various methodologies in recent decades to identify and locate leakages in water, oil and gas supply networks. These methodologies include, among others, the use of acoustic sensors, measurements, abrupt statistical analysis etc. The issue of leak quantification is to estimate, given some observations about that network, the size and location of one or more leaks in a water pipeline network. In detecting background leakage, however, there is a greater uncertainty in using these methodologies since their output is not so reliable. In this work, we are presenting a scalable concept and simulation where a pressure-driven model (PDM) was used to determine water pipeline leakage in a system network. These pressure data were collected with the use of acoustic sensors located at various node points after a predetermined distance apart. We were able to determine with the use of correlation difference to determine the leakage point locally introduced at a predetermined point between two consecutive nodes, causing a substantial pressure difference between in a pipeline network. After de-noising the signal from the sensors at the nodes, we successfully obtained the exact point where we introduced the local leakage using the correlation difference model we developed.

Keywords: leakage detection, acoustic signals, pipeline network, correlation, wireless sensor networks (WSNs)

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Authors: Keltoum Bouherine, Olivier Leroy

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The present work is dedicated to study a three–dimensional (3D) self-consistent fluid simulation of microwave discharges of argon plasma in PECVD reactor. The model solves the Maxwell’s equations, continuity equations for charged species and the electron energy balance equation, coupled with Poisson’s equation, and Navier-Stokes equations by finite element method, using COMSOL Multiphysics software. In this study, the simulations yield the profiles of plasma components as well as the charge densities and electron temperature, the electric field, the gas velocity, and gas temperature. The results show that the microwave plasma reactor is outside of local thermodynamic equilibrium.The present work is dedicated to study a three–dimensional (3D) self-consistent fluid simulation of microwave discharges of argon plasma in PECVD reactor. The model solves the Maxwell’s equations, continuity equations for charged species and the electron energy balance equation, coupled with Poisson’s equation, and Navier-Stokes equations by finite element method, using COMSOL Multiphysics software. In this study, the simulations yield the profiles of plasma components as well as the charge densities and electron temperature, the electric field, the gas velocity, and gas temperature. The results show that the microwave plasma reactor is outside of local thermodynamic equilibrium.

Keywords: electron density, electric field, microwave plasma reactor, gas velocity, non-equilibrium plasma

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Authors: Yuet Wah Echo Yeung

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Working with people from minority ethnic groups, refugees and asylum seeking communities who have limited proficiency in the language of the host country often presents a major challenge for social workers. Because of language differences, social workers need to work with interpreters to ensure accurate information is collected for their assessment and intervention. Drawing from social learning theory, this paper discusses how role play was used as an experiential learning exercise in a training session to help social work students develop skills when working with interpreters. Social learning theory posits that learning is a cognitive process that takes place in a social context when people observe, imitate and model others’ behaviours. The roleplay also helped students understand the role of the interpreter and the challenges they may face when they rely on interpreters to communicate with service users and their family. The first part of the session involved role play. A tutor played the role of social worker and deliberately behaved in an unprofessional manner and used inappropriate body language when working alongside the interpreter during a home visit. The purpose of the roleplay is not to provide a positive role model for students to ‘imitate’ social worker’s behaviours. Rather it aims to active and provoke internal thinking process and encourages students to critically consider the impacts of poor practice on relationship building and the intervention process. Having critically reflected on the implications for poor practice, students were then asked to play the role of social worker and demonstrate what good practice should look like. At the end of the session, students remarked that they learnt a lot by observing the good and bad example; it showed them what not to do. The exercise served to remind students how practitioners can easily slip into bad habits and of the importance of respect for the cultural difference when working with people from different cultural backgrounds.

Keywords: role play, social learning theory, social work practice, working with interpreters

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Authors: Ivan Poza Martínez

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The international energy landscape has been significantly affected by the Covid-19 pandemic and te conflict in Ukraine. The Vaca Muerta sedimentary formation in Argentina´s Neuquén province has become a crucial area for energy production, specifically in the shale gas ad shale oil sectors. The massive investment required for theexploitation of this reserve make it essential to understand te determinants of the investment in the upstream sector at both local ad international levels. The aim of this study is to identify the qualitative and quantitative determinants of investment in Vaca Muerta. The research methodolody employs both quantiative ( econometrics ) and qualitative approaches. A linear regression model is used to analyze the impact in non-conventional hydrocarbons. The study highlights that, in addition to quantitative factors, qualitative variables, particularly the design of a regulatory framework, significantly influence the level of the investment in Vaca Muerta. The analysis reveals the importance of attracting both domestic and foreign capital investment. This research contributes to understanding the factors influencing investment inthe Vaca Muerta regioncomapred to other published studies. It emphasizes to role of qualitative varibles, such as regulatory frameworks, in the development of the shale gas and oil sectors. The study uses a combination ofquantitative data , such a investment figures, and qualitative data, such a regulatory frameworks. The data is collected from various rpeorts and industry publications. The linear regression model is used to analyze the relationship between the variables and the investment in Vaca Muerta. The research addresses the question of what factors drive investment in the Vaca Muerta region, both from a quantitative and qualitative perspective. The study concludes that a combination of quantitative and qualitative factors, including the design of a regulatory framework, plays a significant role in attracting investment in Vaca Muerta. It highlights the importance of these determinants in the developmentof the local energy sector and the potential economic benefits for Argentina and the Southern Cone region.

Keywords: vaca muerta, FDI, shale gas, shale oil, YPF

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Authors: Redhouane Ghernaout, Amira Fredj, Boualem Remini

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Suspended sediment transport is a serious problem worldwide, but it is much more worrying in certain regions of the world, as is the case in the Maghreb and more particularly in Algeria. It continues to take disturbing proportions in Northern Algeria due to the variability of rains in time and in space and constant deterioration of vegetation. Its prediction is essential in order to identify its intensity and define the necessary actions for its reduction. The purpose of this study is to analyze the concentration data of suspended sediment measured at Wadi El-Abtal Hydrometric Station. It also aims to find and highlight regressive power relationships, which can explain the suspended solid flow by the measured liquid flow. The study strives to find models of artificial neural networks linking the flow, month and precipitation parameters with solid flow. The obtained results show that the power function of the solid transport rating curve and the models of artificial neural networks are appropriate methods for analysing and estimating suspended sediment transport in Wadi Mina at Wadi El-Abtal Hydrometric Station. They made it possible to identify in a fairly conclusive manner the model of neural networks with four input parameters: the liquid flow Q, the month and the daily precipitation measured at the representative stations (Frenda 013002 and Ain El-Hadid 013004 ) of the watershed. The model thus obtained makes it possible to estimate the daily solid flows (interpolate and extrapolate) even beyond the period of observation of solid flows (1985/86 to 1999/00), given the availability of the average daily liquid flows and daily precipitation since 1953/1954.

Keywords: suspended sediment, concentration, regression, liquid flow, solid flow, artificial neural network, modeling, mina, algeria

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Authors: Etienne Gaborit, Dorothy Durnford, Daniel Deacu, Marco Carrera, Nathalie Gauthier, Camille Garnaud, Vincent Fortin

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A new experimental streamflow forecasting system was recently implemented at the Environment and Climate Change Canada’s (ECCC) Canadian Centre for Meteorological and Environmental Prediction (CCMEP). It relies on CaLDAS (Canadian Land Data Assimilation System) for the assimilation of surface variables, and on a surface prediction system that feeds a routing component. The surface energy and water budgets are simulated with the SVS (Soil, Vegetation, and Snow) Land-Surface Scheme (LSS) at 2.5-km grid spacing over Canada. The routing component is based on the Watroute routing scheme at 1-km grid spacing for the Great Lakes and Nelson River watersheds. The system is run in two distinct phases: an analysis part and a forecast part. During the analysis part, CaLDAS outputs are used to force the routing system, which performs streamflow assimilation. In forecast mode, the surface component is forced with the Canadian GEM atmospheric forecasts and is initialized with a CaLDAS analysis. Streamflow performances of this new system are presented over 2019. Performances are compared to the current ECCC’s operational streamflow forecasting system, which is different from the new experimental system in many aspects. These new streamflow forecasts are also compared to persistence. Overall, the new streamflow forecasting system presents promising results, highlighting the need for an elaborated assimilation phase before performing the forecasts. However, the system is still experimental and is continuously being improved. Some major recent improvements are presented here and include, for example, the assimilation of snow cover data from remote sensing, a backward propagation of assimilated flow observations, a new numerical scheme for the routing component, and a new reservoir model.

Keywords: assimilation system, distributed physical model, offline hydro-meteorological chain, short-term streamflow forecasts

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Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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