Search results for: network screening
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5837

Search results for: network screening

3287 Mitigating the Negative Health Effects from Stress - A Social Network Analysis

Authors: Jennifer A. Kowalkowski

Abstract:

Production agriculture (farming) is a physically, emotionally, and cognitively stressful occupation, where workers have little control over the stressors that impact both their work and their lives. In an occupation already rife with hazards, these occupational-related stressors have been shown to increase farm workers’ risks for illness, injury, disability, and death associated with their work. Despite efforts to mitigate the negative health effects from occupational-related stress (ORS) and to promote health and well-being (HWB) among farmers in the US, marked improvements have not been attained. Social support accessed through social networks has been shown to buffer against the negative health effects from stress, yet no studies have directly examined these relationships among farmers. The purpose of this study was to use social network analysis to explore the social networks of farm owner-operators and the social supports available to them for mitigating the negative health effects of ORS. A convenience sample of 71 farm owner-operators from a Midwestern County in the US completed and returned a mailed survey (55.5% response rate) that solicited information about their social networks related to ORS. Farmers reported an average of 2.4 individuals in their personal networks and higher levels of comfort discussing ORS with female network members. Farmers also identified few connections (3.4% density) and indicated low comfort with members of affiliation networks specific to ORS. Findings from this study highlighted that farmers accessed different social networks and resources for their personal HWB than for issues related to occupational(farm-related) health and safety. In addition, farmers’ social networks for personal HWB were smaller, with different relational characteristics than reported in studies of farmers’ social networks related to occupational health and safety. Collectively, these findings suggest that farmers conceptualize personal HWB differently than farm health and safety. Therefore, the same research approaches and targets that guide occupational health and safety research may not be appropriate for personal HWB for farmers. Interventions and programming targeting ORS and HWB have largely been offered through the same platforms or mechanisms as occupational health and safety programs. This may be attributed to the significant overlap between the farm as a family business and place of residence, or that ORS stems from farm-related issues. However, these assumptions translated to health research of farmers and farm families from the occupational health and safety literature have not been directly studied or challenged. Thismay explain why past interventions have not been effective at improving health outcomes for farmers and farm families. A close examination of findings from this study raises important questions for researchers who study agricultural health. Findings from this study have significant implications for future research agendas focused on addressing ORS, HWB, and health disparities for farmersand farm families.

Keywords: agricultural health, occupational-related stress, social networks, well-being

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3286 Antioxidative Effect of Bauhinia acuminata Water Extract Consumption in Rat

Authors: Amornnat Thuppia, Pornrut Rabintossaporn, Suphaket Saenthaweesuk, Nuntiya Somparn

Abstract:

The aim of this present study was to determine the antioxidant effects and its mechanism of aqueous leaves extract of Bauhinia acuminata (BA) in rat. The extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with the extract at the dose of 50, 100 and 200 mg/kg for 28 days. Phytochemical screening of plant extracts showed the presence of saponin, alkaloid, cardiac glycosides, flavonoids, tannin and steroid compounds. The extract contained phenolic compounds 53.36 ± 1.01 mg of gallic acid equivalents per gram BA extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 44.47 ± 2.83 µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14µg/mL. In the animals, the extract was well tolerated by the animals throughout the 28 days of study as shown by normal serum levels AST, ALP, ALT, BUN and Cr as well as normal histology of liver and pancreatic and kidney tissue. Significantly, reduction of serum oxidative stress markers malondialdehyde (MDA) was found in rat treated with BA extract compared with control. Taken together, this study provides evidence that Bauhinia acuminata (BA) exhibits direct antioxidant properties and induces cytoprotective enzyme in vivo.

Keywords: Bauhinia acuminata, antioxidant, malondialdehyde (MDA), oxidative marker

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3285 Application of Federated Learning in the Health Care Sector for Malware Detection and Mitigation Using Software-Defined Networking Approach

Authors: A. Dinelka Panagoda, Bathiya Bandara, Chamod Wijetunga, Chathura Malinda, Lakmal Rupasinghe, Chethana Liyanapathirana

Abstract:

This research takes us forward with the concepts of Federated Learning and Software-Defined Networking (SDN) to introduce an efficient malware detection technique and provide a mitigation mechanism to give birth to a resilient and automated healthcare sector network system by also adding the feature of extended privacy preservation. Due to the daily transformation of new malware attacks on hospital Integrated Clinical Environment (ICEs), the healthcare industry is at an undefinable peak of never knowing its continuity direction. The state of blindness by the array of indispensable opportunities that new medical device inventions and their connected coordination offer daily, a factor that should be focused driven is not yet entirely understood by most healthcare operators and patients. This solution has the involvement of four clients in the form of hospital networks to build up the federated learning experimentation architectural structure with different geographical participation to reach the most reasonable accuracy rate with privacy preservation. While the logistic regression with cross-entropy conveys the detection, SDN comes in handy in the second half of the research to stack up the initial development phases of the system with malware mitigation based on policy implementation. The overall evaluation sums up with a system that proves the accuracy with the added privacy. It is no longer needed to continue with traditional centralized systems that offer almost everything but not privacy.

Keywords: software-defined network, federated learning, privacy, integrated clinical environment, decentralized learning, malware detection, malware mitigation

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3284 Study and Calibration of Autonomous UAV Systems with Thermal Sensing Allowing Screening of Environmental Concerns

Authors: Raahil Sheikh, Abhishek Maurya, Priya Gujjar, Himanshu Dwivedi, Prathamesh Minde

Abstract:

UAVs have been an initial member of our environment since it's the first used by Austrian warfare in Venice. At that stage, they were just pilotless balloons equipped with bombs to be dropped on enemy territory. Over time, technological advancements allowed UAVs to be controlled remotely or autonomously. This study shall mainly focus on the intensification of pre-existing manual drones equipping them with a variety of sensors and making them autonomous, and capable, and purposing them for a variety of roles, including thermal sensing, data collection, tracking creatures, forest fires, volcano detection, hydrothermal studies, urban heat, Island measurement, and other environmental research. The system can also be used for reconnaissance, research, 3D mapping, and search and rescue missions. This study mainly focuses on automating tedious tasks and reducing human errors as much as possible, reducing deployment time, and increasing the overall efficiency, efficacy, and reliability of the UAVs. Creation of a comprehensive Ground Control System UI (GCS) enabling less trained professionals to be able to use the UAV with maximum potency. With the inclusion of such an autonomous system, artificially intelligent paths and environmental gusts and concerns can be avoided.

Keywords: UAV, drone, autonomous system, thermal imaging

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3283 Power System Cyber Security Risk in the Era of Digital Transformation

Authors: Rafat Rob, Khaled Alotaibi, Dana Nour, Abdullah Albadrani, Abdulmohsen Mulhim

Abstract:

Power systems digitization solutions provides a comprehensive smart, cohesive, interconnected network, extensive connectivity between digital assets, physical power plants, and resources to form digital economies. However, digitization has exposed the classical air gapped power plants to the rapid spread of cyber threats and attacks in the process delaying and forcing many organizations to rethink their cyber security policies and standards before they can augment their operation the new advanced digital devices. Cyber Security requirements for power systems (and industry control systems therein) demand a new approach, unique methodology, and design process that is completely different to Cyber Security measures designed for the IT systems. In practice, Cyber Security strategy, as applied to power systems, tends to be closely aligned to those measures applied for IT system purposes. The differentiator for Cyber Security in terms of power systems are the physical assets and applications used, alongside the ever-growing rate of expansion within the industry controls sector (in comparison to the relatively saturated growth observed for corporate IT systems). These factors increase the magnitude of the cyber security risk within such systems. The introduction of smart devices and sensors along the grid initiate vulnerable entry points to the systems. Every installed Smart Meter is a target; the way these devices communicate with each other may instigate a Denial of Service (DoS) and Distributed Denial of Service (DDoS) attack. Attacking one sensor or meter has the potential to propagate itself throughout the power grid reaching the IT network, where it may manifest itself as a malware infiltration.

Keywords: supply chain, cybersecurity, maturity model, risk, smart grid

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3282 Assessment of Socio-Economic and Water Related Topics at Community Level in Yatta Town, Palestine

Authors: Nibal Al-Batsh, Issam A. Al-Khatib, Subha Ghannam

Abstract:

Yatta is a town in the Governorate of Hebron, located 9 km south of Hebron City in the West Bank. The town houses over 100,000 people, 49% of which are females; a population that doubles every 15 years. Yatta has been connected to a water network since 1974 serving nearly 85% of the households. The water network is old and inadequate to meet the needs of the population. The water supply made available to the area is also very limited, estimated to be around 20 l/c/d. Residents are thus forced to rely on water vendors which supply water with a lower quality compared to municipal water while being 400% more expensive. As a cheaper and more reliable alternative, rainwater harvesting is a common practice in the area, with the majority of the households owning at least one cistern. Rainwater harvesting is of great socioeconomic importance in areas where water sources are scarce or polluted. In this research, the quality of harvested rainwater used for drinking and domestic purposes in the Yatta area was assessed throughout a year. A total of 100 samples, were collected from (cisterns) with an average capacity of 69 m3, which are adjacent to cement-roof catchment areas with an average area of 145 m2. Samples were analyzed for a number of parameters including: pH, alkalinity, hardness, turbidity, Total Dissolved Solids (TDS), NO3, NH4, chloride and salinity. Biological and microbiological contents such as Total Coliforms (TCC) and Fecal Coliforms (FC) bacteria were also tested. Results showed that most of the rainwater samples were within WHO and EPA guidelines set for chemical parameters. The research also addressed the impact of different socioeconomic attributes on rainwater harvesting through questionnaire that was pre-tested before the actual statically sample is collected.

Keywords: rainwater, harvesting, water quality, socio-economic aspects

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3281 Domestic Violence and Wives’ Depressive Symptoms in China: The Moderating Role of Gender Ideology

Authors: Xiangmei Li

Abstract:

Domestic violence (DV) victims are at a greater risk of suffering mental health problems; however, not all victims experience the same degree of depression. Women respond differently to gender inequalities based on their gender ideologies. This study explored the moderating role of gender ideology in the relation between exposure to DV and depression. Data were drawn from a sub-sample of women aged 18-60 from the Third WaveSurvey on the Social Status of Women in China (N = 10,701). The survey adopted astratified three-stage sampling design to select a representative sample of respondents from the country. Regression models were used to examine the moderating effects of gender ideology on the relation between DV and depression. Women who reported DV experience had more severe depressive symptoms after controlling for confounding social–demographic factors (β = 0.592, 95% CI: 0.489 – 0.695). Women's gender ideology moderated the association between DV severity and depression (β = -0.049, 95% CI: -0.085 – -0.013), despite being subjected to the same levels of victimization. The experience of domestic violence is a useful indicator for routine screening for depression in clinic and community settings. Interventions that aim to decrease depression caused by DV are more likely to be effective if they promote more egalitarian gender ideology to counter the mindset that a woman's role is confined to the home and a family suffers if the wife participates in the labor force.

Keywords: domestic violence against wives, depression, gender ideology, moderation

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3280 Response to Name Training in Autism Spectrum Disorder (ASD): A New Intervention Model

Authors: E. Verduci, I. Aguglia, A. Filocamo, I. Macrì, R. Scala, A. Vinci

Abstract:

One of the first indicator of autism spectrum disorder (ASD) is a decreasing tendency or failure to respond to name (RTN) call. Despite RTN is important for social and language developmentand it’s a common target for early interventions for children with ASD, research on specific treatments is insufficient and does not consider the importance of the discrimination between the own name and other names. The purpose of the current study was to replicate an assessment and treatment model proposed by Conine et al. (2020) to teach children with ASD to respond to their own name and to not respond to other names (RTO). The model includes three different phases (baseline/screening, treatment, and generalization), and itgradually introduces the different treatment components, starting with the most naturalistic ones (such as social interaction) and adding more intrusive components (such as tangible reinforcements, prompt and fading procedures) if necessary. The participants of this study were three children with ASD diagnosis: D. (5 years old) with a low frequency of RTN, M. (7 years old) with a RTN unstable and no ability of discrimination between his name and other names, S. (3 years old) with a strong RTN but a constant response to other names. Moreover, the treatment for D. and M. consisted of social and tangible reinforcements (treatment T1), for S. the purpose of the treatment was to teach the discrimination between his name and the others. For all participants, results suggest the efficacy of the model to acquire the ability to selectively respond to the own name and the generalization of the behavior with other people and settings.

Keywords: response to name, autism spectrum disorder, progressive training, ABA

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3279 Database of Pharmacogenetics HLA-A*31:01 Allele in Thai Population and Carbamazepine-Induced SCARs

Authors: Watchawin Ekphinitphithaya, Patompong Satapornpong

Abstract:

Introduction: Carbamazepine (CBZ) is one of the most prescribed antiepileptic drugs (AEDs) by neurologists and non-neurologist worldwide. CBZ is usually prescribed along with other drugs, leading to the possibility of severe cutaneous adverse drug reactions (SCARs). The HLA-B*15:02 is strongly associated with CBZ-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations, while HLA-A*31:01 allele has been reported to be associated with CBZ-induced SCARs in European population and Japanese. Objective: The aim of this study is to investigate the distribution of pharmacogenetics HLA-A*31:01 marker in a healthy Thai population associated with Carbamazepine-induced SCARs. Materials and Methods: Prospective study, 350 unrelated healthy Thais were recruited in this study. Human leukocyte antigen-A alleles were genotyped using PCR-sequence specific oligonucleotides (PCR-SSOs). Results: The frequency of HLA-A alleles were HLA-A*11:01 (190 alleles, 27.14%), HLA-A*24:02 (82 alleles, 11.71%), HLA-A*02:03 (80 alleles, 11.43%), HLA-A*33:03 (76 alleles, 10.86%), HLA-A*02:07 (58 alleles, 8.29%), HLA-A*02:01 (35 alleles, 5.00%), HLA-A*24:07 (29 alleles, 4.14%), HLA-A*02:06 – HLA-A*30:01 (15 alleles, 2.14%), and HLA-A*01:01 (14 alleles, 2.00%). Particularly, the number of HLA-A*31:01 alleles was 6 of 700 (0.86%) in the healthy Thai population. Many research presented varying distributions of HLA-A*31:01 in Asians, including 2% of Han Chinese, 9% of Japanese and 5% of Koreans. In addition, this allele was found approximately 2-5% in the Caucasian population. Conclusions: Thus, the pharmacogenetics database is vital to support in many populations, especially in Thais, for screening HLA-A*31:01 allele to avoid CBZ-induced SCARs before initiating treatments in each population.

Keywords: Carbamazepine, HLA-A*31:01, Thai population, pharmacogenetics

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3278 Evaluation of Short-Term Load Forecasting Techniques Applied for Smart Micro-Grids

Authors: Xiaolei Hu, Enrico Ferrera, Riccardo Tomasi, Claudio Pastrone

Abstract:

Load Forecasting plays a key role in making today's and future's Smart Energy Grids sustainable and reliable. Accurate power consumption prediction allows utilities to organize in advance their resources or to execute Demand Response strategies more effectively, which enables several features such as higher sustainability, better quality of service, and affordable electricity tariffs. It is easy yet effective to apply Load Forecasting at larger geographic scale, i.e. Smart Micro Grids, wherein the lower available grid flexibility makes accurate prediction more critical in Demand Response applications. This paper analyses the application of short-term load forecasting in a concrete scenario, proposed within the EU-funded GreenCom project, which collect load data from single loads and households belonging to a Smart Micro Grid. Three short-term load forecasting techniques, i.e. linear regression, artificial neural networks, and radial basis function network, are considered, compared, and evaluated through absolute forecast errors and training time. The influence of weather conditions in Load Forecasting is also evaluated. A new definition of Gain is introduced in this paper, which innovatively serves as an indicator of short-term prediction capabilities of time spam consistency. Two models, 24- and 1-hour-ahead forecasting, are built to comprehensively compare these three techniques.

Keywords: short-term load forecasting, smart micro grid, linear regression, artificial neural networks, radial basis function network, gain

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3277 Evaluation of Railway Network and Service Performance Based on Transportation Sustainability in DKI Jakarta

Authors: Nur Bella Octoria Bella, Ayomi Dita Rarasati

Abstract:

DKI Jakarta is Indonesia's capital city with the 10th highest congestion rate in the world based on the 2019 traffic index. Other than that based on World Air Quality Report in 2019 showed DKI Jakarta's air pollutant concentrate 49.4 µg and the 5th highest air pollutant in the world. In the urban city nowadays, the mobility rate is high enough and the efficiency for sustainability assessment in transport infrastructure development is needed. This efficiency is the important key for sustainable infrastructure development. DKI Jakarta is nowadays in the process of constructing the railway infrastructure to support the transportation system. The problems appearing are the railway infrastructure networks and the service in DKI Jakarta already planned based on sustainability factors or not. Therefore, the aim of this research is to make the evaluation of railways infrastructure networks performance and services in DKI Jakarta regards on the railway sustainability key factors. Further, this evaluation will be used to make the railway sustainability assessment framework and to offer some of the alternative solutions to improve railway transportation sustainability in DKI Jakarta. Firstly a very detailed literature review of papers that have focused on railway sustainability factors and their improvements of railway sustainability, published in the scientific journal in the period 2011 until 2021. Regarding the sustainability factors from the literature review, further, it is used to assess the current condition of railway infrastructure in DKI Jakarta. The evaluation will be using a Likert rate questionnaire and directed to the transportation railway expert and the passenger. Furthermore, the mapping and evaluation rate based on the sustainability factors will be compared to the effect factors using the Analytical Hierarchical Process (AHP). This research offers the network's performance and service rate impact on the sustainability aspect and the passenger willingness for using the rail public transportation in DKI Jakarta.

Keywords: transportation sustainability, railway transportation, sustainability, DKI Jakarta

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3276 Prediction of Coronary Artery Stenosis Severity Based on Machine Learning Algorithms

Authors: Yu-Jia Jian, Emily Chia-Yu Su, Hui-Ling Hsu, Jian-Jhih Chen

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Coronary artery is the major supplier of myocardial blood flow. When fat and cholesterol are deposit in the coronary arterial wall, narrowing and stenosis of the artery occurs, which may lead to myocardial ischemia and eventually infarction. According to the World Health Organization (WHO), estimated 740 million people have died of coronary heart disease in 2015. According to Statistics from Ministry of Health and Welfare in Taiwan, heart disease (except for hypertensive diseases) ranked the second among the top 10 causes of death from 2013 to 2016, and it still shows a growing trend. According to American Heart Association (AHA), the risk factors for coronary heart disease including: age (> 65 years), sex (men to women with 2:1 ratio), obesity, diabetes, hypertension, hyperlipidemia, smoking, family history, lack of exercise and more. We have collected a dataset of 421 patients from a hospital located in northern Taiwan who received coronary computed tomography (CT) angiography. There were 300 males (71.26%) and 121 females (28.74%), with age ranging from 24 to 92 years, and a mean age of 56.3 years. Prior to coronary CT angiography, basic data of the patients, including age, gender, obesity index (BMI), diastolic blood pressure, systolic blood pressure, diabetes, hypertension, hyperlipidemia, smoking, family history of coronary heart disease and exercise habits, were collected and used as input variables. The output variable of the prediction module is the degree of coronary artery stenosis. The output variable of the prediction module is the narrow constriction of the coronary artery. In this study, the dataset was randomly divided into 80% as training set and 20% as test set. Four machine learning algorithms, including logistic regression, stepwise regression, neural network and decision tree, were incorporated to generate prediction results. We used area under curve (AUC) / accuracy (Acc.) to compare the four models, the best model is neural network, followed by stepwise logistic regression, decision tree, and logistic regression, with 0.68 / 79 %, 0.68 / 74%, 0.65 / 78%, and 0.65 / 74%, respectively. Sensitivity of neural network was 27.3%, specificity was 90.8%, stepwise Logistic regression sensitivity was 18.2%, specificity was 92.3%, decision tree sensitivity was 13.6%, specificity was 100%, logistic regression sensitivity was 27.3%, specificity 89.2%. From the result of this study, we hope to improve the accuracy by improving the module parameters or other methods in the future and we hope to solve the problem of low sensitivity by adjusting the imbalanced proportion of positive and negative data.

Keywords: decision support, computed tomography, coronary artery, machine learning

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3275 1,8-Naphthalimide Substituted 4,4-Difluoroboradiaza-S-Indacene Dyads: Synthesis, Structure, Properties and Live-Cell Imaging

Authors: Madhurima Poddar, Vinay Sharma, Shaikh M. Mobin, Rajneesh Misra

Abstract:

Three 1,8-naphthalimide (NPI) substituted 4,4-difluoroboradiaza-s-indacene (BODIPY) dyads were synthesized via Pd-catalyzed Sonogashira cross-coupling reaction of ethynyl substituted NPI with the meso-, β- and α-halogenated BODIPYs, respectively. The photophysical and electrochemical data reveals considerable electronic communication between the BODIPY and NPI moieties. The electronic absorption spectrum reveals that the substitution of NPI at α position of BODIPY exhibit better electronic communication between the NPI and the BODIPY units. The electronic structures of all the dyads exhibit planar geometries which are in a good correlation with the structures obtained from single crystal X-ray diffraction. The crystal structures of the dyads exhibit interesting supramolecular interactions. The dyads show good cytocompatibility with the potential of multicolor live-cell imaging; making them excellent candidates for biological applications. The work provides an important strategy of screening the substitution pattern at different position of BODIPYs which will be useful for the design of BODIPY based organic molecules for various optoelectronic applications as well as bio-imaging.

Keywords: bio-imaging studies, cross-coupling, cyclic voltammetry, density functional calculations, fluorescence spectra, single crystal XRD, UV/Vis spectroscopy

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3274 Digital Platforms: Creating Value through Network Effects under Pandemic Conditions

Authors: S. Łęgowik-Świącik

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This article is a contribution to the research into the determinants of value creation via digital platforms in variable operating conditions. The dynamics of the market environment caused by the COVID-19 pandemic have made enterprises built on digital platforms financially successful. While many classic companies are struggling with the uncertainty of conducting a business and difficulties in the process of value creation, digital platforms create value by modifying the existing business model to meet the changing needs of customers. Therefore, the objective of this publication is to understand and explain the relationship between value creation and the conversion of the business model built on digital platforms under pandemic conditions. The considerations relating to the conceptual framework and determining the research objective allowed for adopting the hypothesis, assuming that the processes of value creation are evolving, and the measurement of these processes allows for the protection of value created and enables its growth in changing circumstances. The research methods, such as critical literature analysis and case study, were applied to accomplish the objective pursued and verify the hypothesis formulated. The empirical research was carried out based on the data from enterprises listed on the Nasdaq Stock Exchange: Amazon, Alibaba, and Facebook. The research period was the years 2018-2021. The surveyed enterprises were chosen based on the targeted selection. The problem discussed is important and current since the lack of in-depth theoretical research results in few attempts to identify the determinants of value creation via digital platforms. The above arguments led to an attempt at theoretical analysis and empirical research to fill in the gap perceived by deepening the understanding of the process of value creation through network effects via digital platforms under pandemic conditions.

Keywords: business model, digital platforms, enterprise management, pandemic conditions, value creation process

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3273 A Multilayer Perceptron Neural Network Model Optimized by Genetic Algorithm for Significant Wave Height Prediction

Authors: Luis C. Parra

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The significant wave height prediction is an issue of great interest in the field of coastal activities because of the non-linear behavior of the wave height and its complexity of prediction. This study aims to present a machine learning model to forecast the significant wave height of the oceanographic wave measuring buoys anchored at Mooloolaba of the Queensland Government Data. Modeling was performed by a multilayer perceptron neural network-genetic algorithm (GA-MLP), considering Relu(x) as the activation function of the MLPNN. The GA is in charge of optimized the MLPNN hyperparameters (learning rate, hidden layers, neurons, and activation functions) and wrapper feature selection for the window width size. Results are assessed using Mean Square Error (MSE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE). The GAMLPNN algorithm was performed with a population size of thirty individuals for eight generations for the prediction optimization of 5 steps forward, obtaining a performance evaluation of 0.00104 MSE, 0.03222 RMSE, 0.02338 MAE, and 0.71163% of MAPE. The results of the analysis suggest that the MLPNNGA model is effective in predicting significant wave height in a one-step forecast with distant time windows, presenting 0.00014 MSE, 0.01180 RMSE, 0.00912 MAE, and 0.52500% of MAPE with 0.99940 of correlation factor. The GA-MLP algorithm was compared with the ARIMA forecasting model, presenting better performance criteria in all performance criteria, validating the potential of this algorithm.

Keywords: significant wave height, machine learning optimization, multilayer perceptron neural networks, evolutionary algorithms

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3272 Solar Power Generation in a Mining Town: A Case Study for Australia

Authors: Ryan Chalk, G. M. Shafiullah

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Climate change is a pertinent issue facing governments and societies around the world. The industrial revolution has resulted in a steady increase in the average global temperature. The mining and energy production industries have been significant contributors to this change prompting government to intervene by promoting low emission technology within these sectors. This paper initially reviews the energy problem in Australia and the mining sector with a focus on the energy requirements and production methods utilised in Western Australia (WA). Renewable energy in the form of utility-scale solar photovoltaics (PV) provides a solution to these problems by providing emission-free energy which can be used to supplement the existing natural gas turbines in operation at the proposed site. This research presents a custom renewable solution for the mining site considering the specific township network, local weather conditions, and seasonal load profiles. A summary of the required PV output is presented to supply slightly over 50% of the towns power requirements during the peak (summer) period, resulting in close to full coverage in the trench (winter) period. Dig Silent Power Factory Software has been used to simulate the characteristics of the existing infrastructure and produces results of integrating PV. Large scale PV penetration in the network introduce technical challenges, that includes; voltage deviation, increased harmonic distortion, increased available fault current and power factor. Results also show that cloud cover has a dramatic and unpredictable effect on the output of a PV system. The preliminary analyses conclude that mitigation strategies are needed to overcome voltage deviations, unacceptable levels of harmonics, excessive fault current and low power factor. Mitigation strategies are proposed to control these issues predominantly through the use of high quality, made for purpose inverters. Results show that use of inverters with harmonic filtering reduces the level of harmonic injections to an acceptable level according to Australian standards. Furthermore, the configuration of inverters to supply active and reactive power assist in mitigating low power factor problems. Use of FACTS devices; SVC and STATCOM also reduces the harmonics and improve the power factor of the network, and finally, energy storage helps to smooth the power supply.

Keywords: climate change, mitigation strategies, photovoltaic (PV), power quality

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3271 Monitor Vehicle Speed Using Internet of Things Based Wireless Sensor Network System

Authors: Akber Oumer Abdurezak

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Road traffic accident is a major problem in Ethiopia, resulting in the deaths of many people and potential injuries and crash every year and loss of properties. According to the Federal Transport Authority, one of the main causes of traffic accident and crash in Ethiopia is over speeding. Implementation of different technologies is used to monitor the speed of vehicles in order to minimize accidents and crashes. This research aimed at designing a speed monitoring system to monitor the speed of travelling vehicles and movements, reporting illegal speeds or overspeeding vehicles to the concerned bodies. The implementation of the system is through a wireless sensor network. The proposed system can sense and detect the movement of vehicles, process, and analysis the data obtained from the sensor and the cloud system. The data is sent to the central controlling server. The system contains accelerometer and gyroscope sensors to sense and collect the data of the vehicle. Arduino to process the data and Global System for Mobile Communication (GSM) module for communication purposes to send the data to the concerned body. When the speed of the vehicle exceeds the allowable speed limit, the system sends a message to database as “over speeding”. Both accelerometer and gyroscope sensors are used to collect acceleration data. The acceleration data then convert to speed, and the corresponding speed is checked with the speed limit, and those above the speed limit are reported to the concerned authorities to avoid frequent accidents. The proposed system decreases the occurrence of accidents and crashes due to overspeeding and can be used as an eye opener for the implementation of other intelligent transport system technologies. This system can also integrate with other technologies like GPS and Google Maps to obtain better output.

Keywords: accelerometer, IOT, GSM, gyroscope

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3270 SkyCar Rapid Transit System: An Integrated Approach of Modern Transportation Solutions in the New Queen Elizabeth Quay, Perth, Western Australia

Authors: Arfanara Najnin, Michael W. Roach, Jr., Dr. Jianhong Cecilia Xia

Abstract:

The SkyCar Rapid Transit System (SRT) is an innovative intelligent transport system for the sustainable urban transport system. This system will increase the urban area network connectivity and decrease urban area traffic congestion. The SRT system is designed as a suspended Personal Rapid Transit (PRT) system that travels under a guideway 5m above the ground. A driver-less passenger is via pod-cars that hang from slender beams supported by columns that replace existing lamp posts. The beams are setup in a series of interconnecting loops providing non-stop travel from beginning to end to assure journey time. The SRT forward movement is effected by magnetic motors built into the guideway. Passenger stops are at either at line level 5m above the ground or ground level via a spur guideway that curves off the main thoroughfare. The main objective of this paper is to propose an integrated Automated Transit Network (ATN) technology for the future intelligent transport system in the urban built environment. To fulfil the objective a 4D simulated model in the urban built environment has been proposed by using the concept of SRT-ATN system. The methodology for the design, construction and testing parameters of a Technology Demonstrator (TD) for proof of concept and a Simulator (S) has been demonstrated. The completed TD and S will provide an excellent proving ground for the next development stage, the SRT Prototype (PT) and Pilot System (PS). This paper covered by a 4D simulated model in the virtual built environment is to effectively show how the SRT-ATN system works. OpenSim software has been used to develop the model in a virtual environment, and the scenario has been simulated to understand and visualize the proposed SkyCar Rapid Transit Network model. The SkyCar system will be fabricated in a modular form which is easily transported. The system would be installed in increasingly congested city centers throughout the world, as well as in airports, tourist resorts, race tracks and other special purpose for the urban community. This paper shares the lessons learnt from the proposed innovation and provides recommendations on how to improve the future transport system in urban built environment. Safety and security of passengers are prime factors to be considered for this transit system. Design requirements to meet the safety needs to be part of the research and development phase of the project. Operational safety aspects would also be developed during this period. The vehicles, the track and beam systems and stations are the main components that need to be examined in detail for safety and security of patrons. Measures will also be required to protect columns adjoining intersections from errant vehicles in vehicular traffic collisions. The SkyCar Rapid Transit takes advantage of all current disruptive technologies; batteries, sensors and 4G/5G communication and solar energy technologies which will continue to reduce the costs and make the systems more profitable. SkyCar's energy consumption is extremely low compared to other transport systems.

Keywords: SkyCar, rapid transit, Intelligent Transport System (ITS), Automated Transit Network (ATN), urban built environment, 4D Visualization, smart city

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3269 Non-Revenue Water Management in Palestine

Authors: Samah Jawad Jabari

Abstract:

Water is the most important and valuable resource not only for human life but also for all living things on the planet. The water supply utilities should fulfill the water requirement quantitatively and qualitatively. Drinking water systems are exposed to both natural (hurricanes and flood) and manmade hazards (risks) that are common in Palestine. Non-Revenue Water (NRW) is a manmade risk which remains a major concern in Palestine, as the NRW levels are estimated to be at a high level. In this research, Hebron city water distribution network was taken as a case study to estimate and audit the NRW levels. The research also investigated the state of the existing water distribution system in the study area by investigating the water losses and obtained more information on NRW prevention and management practices. Data and information have been collected from the Palestinian Water Authority (PWA) and Hebron Municipality (HM) archive. In addition to that, a questionnaire has been designed and administered by the researcher in order to collect the necessary data for water auditing. The questionnaire also assessed the views of stakeholder in PWA and HM (staff) on the current status of the NRW in the Hebron water distribution system. The important result obtained by this research shows that NRW in Hebron city was high and in excess of 30%. The main factors that contribute to NRW were the inaccuracies in billing volumes, unauthorized consumption, and the method of estimating consumptions through faulty meters. Policy for NRW reduction is available in Palestine; however, it is clear that the number of qualified staff available to carry out the activities related to leak detection is low, and that there is a lack of appropriate technologies to reduce water losses and undertake sufficient system maintenance, which needs to be improved to enhance the performance of the network and decrease the level of NRW losses.

Keywords: non-revenue water, water auditing, leak detection, water meters

Procedia PDF Downloads 279
3268 Efficacy of the ExVent Accessory with the O2Vent Optima Oral Appliance in the Treatment of Obstructive Sleep Apnea: A Clinical Trial

Authors: Sat Sharma, Antonella Conflitti, Hilary Reiter

Abstract:

Introduction: The study's purpose was to assess the efficacy of the oral appliance device O2Vent Optima + ExVent as compared to Optima in the treatment of OSA. Methods: A prospective, open-label study conducted at 3 sites included subjects with mild to moderate OSA (AHI ≥ 5 and ≤ 30). Screening Phase: A diagnostic in-lab PSG study was performed to confirm a diagnosis of mild to moderate OSA. Treatment I: Subjects used O2Vent Optima for 6 weeks and underwent an in-lab PSG sleep night while using the O2Vent Optima. Treatment II: Subjects used O2Vent Optima + ExVent for 6 weeks and underwent an in-lab PSG sleep night while using the O2Vent Optima + ExVent Primary Effectiveness Measure: Change in AHI between baseline vs. O2Vent Optima MAD vs. O2Vent Optima + ExVent. Results: Treatment with Optima, Optima + ExVent reduced AHI from 22.5±6.4/hr to 12.6±4.5/hr to 5.9±2.7 (p< 0.005 baseline vs. Optima and Optima + ExVent; p<0.05 Optima MAD vs. Optima + ExVent). The average reduction in AHI with Optima was 43%, and with Optima + ExVent was 72%. The lowest oxygen during sleep increased from 84.6±2.7% to 88.6±2.9% to 91.6±3.2% (p< 0.005 baseline vs. Optima and Optima + ExVent; p<0.05 Optima vs. Optima + ExVent). During the trial, patients on treatment with Optima and Optima + ExVent demonstrated no excessive adverse events or device malfunction. Conclusion: Treatment with O2Vent Optima and O2Vent Optima + ExVent significantly improved OSA compared to the baseline. An even greater benefit was observed with the addition of ExVent to the Optima in mild to moderate OSA.

Keywords: oral appliance, O2Vent, sleep dentistry, sleep apnea

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3267 Reservoir-Triggered Seismicity of Water Level Variation in the Lake Aswan

Authors: Abdel-Monem Sayed Mohamed

Abstract:

Lake Aswan is one of the largest man-made reservoirs in the world. The reservoir began to fill in 1964 and the level rose gradually, with annual irrigation cycles, until it reached a maximum water level of 181.5 m in November 1999, with a capacity of 160 km3. The filling of such large reservoir changes the stress system either through increasing vertical compressional stress by loading and/or increased pore pressure through the decrease of the effective normal stress. The resulted effect on fault zones changes stability depending strongly on the orientation of pre-existing stress and geometry of the reservoir/fault system. The main earthquake occurred on November 14, 1981, with magnitude 5.5. This event occurred after 17 years of the reservoir began to fill, along the active part of the Kalabsha fault and located not far from the High Dam. Numerous of small earthquakes follow this earthquake and continue till now. For this reason, 13 seismograph stations (radio-telemetry network short-period seismometers) were installed around the northern part of Lake Aswan. The main purpose of the network is to monitor the earthquake activity continuously within Aswan region. The data described here are obtained from the continuous record of earthquake activity and lake-water level variation through the period from 1982 to 2015. The seismicity is concentrated in the Kalabsha area, where there is an intersection of the easterly trending Kalabsha fault with the northerly trending faults. The earthquake foci are distributed in two seismic zones, shallow and deep in the crust. Shallow events have focal depths of less than 12 km while deep events extend from 12 to 28 km. Correlation between the seismicity and the water level variation in the lake provides great suggestion to distinguish the micro-earthquakes, particularly, those in shallow seismic zone in the reservoir–triggered seismicity category. The water loading is one factor from several factors, as an activating medium in triggering earthquakes. The common factors for all cases of induced seismicity seem to be the presence of specific geological conditions, the tectonic setting and water loading. The role of the water loading is as a supplementary source of earthquake events. So, the earthquake activity in the area originated tectonically (ML ≥ 4) and the water factor works as an activating medium in triggering small earthquakes (ML ≤ 3). Study of the inducing seismicity from the water level variation in Aswan Lake is of great importance and play great roles necessity for the safety of the High Dam body and its economic resources.

Keywords: Aswan lake, Aswan seismic network, seismicity, water level variation

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3266 Mutations in the GJB2 Gene Are the Cause of an Important Number of Non-Syndromic Deafness Cases

Authors: Habib Onsori, Somayeh Akrami, Mohammad Rahmati

Abstract:

Deafness is the most common sensory disorder with the frequency of 1/1000 in many populations. Mutations in the GJB2 (CX26) gene at the DFNB1 locus on chromosome 13q12 are associated with congenital hearing loss. Approximately 80% of congenital hearing loss cases are recessively inherited and 15% dominantly inherited. Mutations of the GJB2 gene, encoding gap junction protein Connexin 26 (Cx26), are the most common cause of hereditary congenital hearing loss in many countries. This report presents two cases of different mutations from Iranian patients with bilateral hearing loss. DNA studies were performed for the GJB2 gene by PCR and sequencing methods. In one of them, direct sequencing of the gene showed a heterozygous T→C transition at nucleotide 604 resulting in a cysteine to arginine amino acid substitution at codon 202 (C202R) in the fourth extracellular domain (TM4) of the protein. The analyses indicate that the C202R mutation appeared de novo in the proband with a possible dominant effect (GenBank: KF 638275). In the other one, DNA sequencing revealed a compound heterozygous mutation (35delG, 363delC) in the Cx26 gene that is strongly associated with congenital non-syndromic hearing loss (NSHL). So screening the mutations for hearing loss individuals referring to genetics counseling centers before marriage and or pregnancy is recommended.

Keywords: CX26, deafness, GJB2, mutation

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3265 Refinement of Existing Benzthiazole lead Targeting Lysine Aminotransferase in Dormant Stage of Mycobacterium tuberculosis

Authors: R. Reshma srilakshmi, S. Shalini, P. Yogeeswari, D. Sriram

Abstract:

Lysine aminotransferase is a crucial enzyme for dormancy in M. tuberculosis. It is involved in persistence and antibiotic resistance. In present work, we attempted to develop benzthiazole derivatives as lysine aminotransferase inhibitors. In our attempts, we also unexpectedly arrived at an interesting compound 21 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)benzoic acid which even though has moderate activity against persistent phase of mycobacterium, it has significant potency against active phase. In the entire series compound 22 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)isophthalic acid emerged as potent molecule with LAT IC50 of 2.62 µM. It has a significant log reduction of 2.9 and 2.3 fold against nutrient starved and biofilm forming mycobacteria. It was found to be inactive in MABA assay and M.marinum induced zebra fish model. It is also devoid of cytotoxicity. Compound 22 was also found to possess bactericidal effect which is independent of concentration and time. It was found to be effective in combination with Rifampicin in 3D granuloma model. The results are very encouraging as the hit molecule shows activity against active as well as persistent forms of tuberculosis. The identified hit needs further more pharmacokinetic and dynamic screening for development as new drug candidate.

Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation

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3264 Development and State in Brazil: How Do Some Institutions Think and Influence These Issues

Authors: Alessandro Andre Leme

Abstract:

To analyze three Brazilian think tanks: a) Fernando Henrique Foundation; b) Celso Furtado International Center; c) Millennium Institute and how they dispute interpretations about the type of development and State that should be adopted in Brazil. We will make use of Network and content analysis of the sites. The analyzes show a dispute that goes from a defense of ultraliberalism to developmentalism, going through a hybrid between State and Market voiced in each of the Think Tanks.

Keywords: sociopolitical and economic thinking, development, strategies, intellectuals, state

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3263 Antimicrobial Activity of Seed Oil of Garlic and Moringa oleifera against Some Food-Borne Microorganisms

Authors: Mansur Abdulrasheed, Ibrahim I. Hussein, Ahmed M. Mubarak, Ahmed F. Umar

Abstract:

This study was aimed at evaluating the phytochemical constituents and the antimicrobial activity of the seed oil of Moringa oleifera and garlic against some selected food-borne microorganisms (Staphylococcus aureus, Escherichia coli, Salmonella spp and Pseudomonas aeruginosa) using disc diffusion method. The results of the phytochemical screening revealed differences in the presence of the phytochemicals among the extracts. Saponins were detected in both Moringa oleifera and garlic seed oil, while alkaloid and tannins were observed in seed oil of garlic. Furthermore, the antibacterial assay results show that the seed oil of Moringa oleifera was inactive against all the tested organisms, even at 100 % concentration. In contrast, garlic oil was found to be active against all the tested organisms. The highest inhibition was observed in E. coli (12 mm) at 100 % concentration, while at 20 % concentration, Salmonella Sp and P. aeruginosa showed the least inhibiton (6 mm). The antimicrobial activity of the seed oil of garlic may be attributed to its phytochemicals components which were not detected in the seed oil of Moringa oleifera. The results of this study have shown the potentials of the seed oil of garlic as an antimicrobial agent more especially in foods, by inhibiting the growth of the test organisms, which range from food-borne pathogens to food spoilage organisms.

Keywords: antimicrobial, garlic, Moringa oleifera, food borne pathogens

Procedia PDF Downloads 486
3262 Infestations of Olive Fruit Fly, Bactrocera oleae (Rossi) (Diptera: Tephritidae), in Different Olive Cultivars in Çanakkale, Turkey

Authors: Hanife Genç

Abstract:

The olive fruit fly, Bactrocera oleae (Rossi), is an economically important and endemic pest in olive (Oleae europae) orchards in Turkey. The aim of this study was to determine olive fruit fly infestation in different olive cultivars in the laboratory. Olive fly infested fruits were collected in Çanakkale province to establish wild fly population. After having reproductive olive fly colonies, 14 olive cultivars were tested in the controlled laboratory conditions, at 23±2 °C, 65% RH and 16:8 h (light: dark) photoperiod. The olive samples from 14 different olive cultivars were collected in October 2015, in Campus of Dardanos, Çanakkale Onsekiz Mart University. Observations were carried out detecting some biological parameters such as the number of oviposition stings, active infestation, total infestation, the number of pupae and the adult emergence. The results indicated that oviposition stings were not associated with pupal yield. A few pupae were found within olive fruits which were not able to exit. Screening of the varieties suggested that less susceptible cultivar to olive fruit fly attacks was Arbequin while Gemlik-2M 2/3 showed significant susceptibility. Ovipositional preference of olive fly females and the success of larval development in different olive varieties are crucial for establishing new olive orchards to prevent high olive fruit fly infestation.

Keywords: infestation, olive fruit fly, olive cultivars, oviposition sting

Procedia PDF Downloads 203
3261 A Multi-Stage Learning Framework for Reliable and Cost-Effective Estimation of Vehicle Yaw Angle

Authors: Zhiyong Zheng, Xu Li, Liang Huang, Zhengliang Sun, Jianhua Xu

Abstract:

Yaw angle plays a significant role in many vehicle safety applications, such as collision avoidance and lane-keeping system. Although the estimation of the yaw angle has been extensively studied in existing literature, it is still the main challenge to simultaneously achieve a reliable and cost-effective solution in complex urban environments. This paper proposes a multi-stage learning framework to estimate the yaw angle with a monocular camera, which can deal with the challenge in a more reliable manner. In the first stage, an efficient road detection network is designed to extract the road region, providing a highly reliable reference for the estimation. In the second stage, a variational auto-encoder (VAE) is proposed to learn the distribution patterns of road regions, which is particularly suitable for modeling the changing patterns of yaw angle under different driving maneuvers, and it can inherently enhance the generalization ability. In the last stage, a gated recurrent unit (GRU) network is used to capture the temporal correlations of the learned patterns, which is capable to further improve the estimation accuracy due to the fact that the changes of deflection angle are relatively easier to recognize among continuous frames. Afterward, the yaw angle can be obtained by combining the estimated deflection angle and the road direction stored in a roadway map. Through effective multi-stage learning, the proposed framework presents high reliability while it maintains better accuracy. Road-test experiments with different driving maneuvers were performed in complex urban environments, and the results validate the effectiveness of the proposed framework.

Keywords: gated recurrent unit, multi-stage learning, reliable estimation, variational auto-encoder, yaw angle

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3260 Credit Card Fraud Detection with Ensemble Model: A Meta-Heuristic Approach

Authors: Gong Zhilin, Jing Yang, Jian Yin

Abstract:

The purpose of this paper is to develop a novel system for credit card fraud detection based on sequential modeling of data using hybrid deep learning models. The projected model encapsulates five major phases are pre-processing, imbalance-data handling, feature extraction, optimal feature selection, and fraud detection with an ensemble classifier. The collected raw data (input) is pre-processed to enhance the quality of the data through alleviation of the missing data, noisy data as well as null values. The pre-processed data are class imbalanced in nature, and therefore they are handled effectively with the K-means clustering-based SMOTE model. From the balanced class data, the most relevant features like improved Principal Component Analysis (PCA), statistical features (mean, median, standard deviation) and higher-order statistical features (skewness and kurtosis). Among the extracted features, the most optimal features are selected with the Self-improved Arithmetic Optimization Algorithm (SI-AOA). This SI-AOA model is the conceptual improvement of the standard Arithmetic Optimization Algorithm. The deep learning models like Long Short-Term Memory (LSTM), Convolutional Neural Network (CNN), and optimized Quantum Deep Neural Network (QDNN). The LSTM and CNN are trained with the extracted optimal features. The outcomes from LSTM and CNN will enter as input to optimized QDNN that provides the final detection outcome. Since the QDNN is the ultimate detector, its weight function is fine-tuned with the Self-improved Arithmetic Optimization Algorithm (SI-AOA).

Keywords: credit card, data mining, fraud detection, money transactions

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3259 Construction and Optimization of Green Infrastructure Network in Mountainous Counties Based on Morphological Spatial Pattern Analysis and Minimum Cumulative Resistance Models: A Case Study of Shapingba District, Chongqing

Authors: Yuning Guan

Abstract:

Under the background of rapid urbanization, mountainous counties need to break through mountain barriers for urban expansion due to undulating topography, resulting in ecological problems such as landscape fragmentation and reduced biodiversity. Green infrastructure networks are constructed to alleviate the contradiction between urban expansion and ecological protection, promoting the healthy and sustainable development of urban ecosystems. This study applies the MSPA model, the MCR model and Linkage Mapper Tools to identify eco-sources and eco-corridors in the Shapingba District of Chongqing and combined with landscape connectivity assessment and circuit theory to delineate the importance levels to extract ecological pinch point areas on the corridors. The results show that: (1) 20 ecological sources are identified, with a total area of 126.47 km², accounting for 31.88% of the study area, and showing a pattern of ‘one core, three corridors, multi-point distribution’. (2) 37 ecological corridors are formed in the area, with a total length of 62.52km, with a ‘more in the west, less in the east’ pattern. (3) 42 ecological pinch points are extracted, accounting for 25.85% of the length of the corridors, which are mainly distributed in the eastern new area. Accordingly, this study proposes optimization strategies for sub-area protection of ecological sources, grade-level construction of ecological corridors, and precise restoration of ecological pinch points.

Keywords: green infrastructure network, morphological spatial pattern, minimal cumulative resistance, mountainous counties, circuit theory, shapingba district

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3258 Pharmacophore-Based Modeling of a Series of Human Glutaminyl Cyclase Inhibitors to Identify Lead Molecules by Virtual Screening, Molecular Docking and Molecular Dynamics Simulation Study

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

Abstract:

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

Procedia PDF Downloads 124