Search results for: hybrid working models
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 11192

Search results for: hybrid working models

2882 Economic Factors Affecting Greenfield Petroleum Refinery and Petrochemical Projects in Africa

Authors: Daniel Muwooya

Abstract:

This paper analyses economic factors that have affected the competitiveness of petroleum refinery and petrochemical projects in sub-Saharan Africa in the past and continue to plague greenfield projects today. Traditional factors like plant sizing and complexity, low-capacity utilization, changing regulatory environment, and tighter product specifications have been important in the past. Additional factors include the development of excess refinery capacity in Asia and the growth of renewable sources of energy – especially for transportation. These factors create both challenges and opportunities for the development of greenfield refineries and petrochemical projects in areas of increased demand growth and new low-cost crude oil production – like sub-Saharan Africa. This paper evaluates the strategies available to project developers and host countries to address contemporary issues of energy transition and the apparent reduction of funds available for greenfield oil and gas projects. The paper also evaluates the structuring of greenfield refinery and petrochemical projects for limited recourse project finance bankability. The methodology of this paper includes analysis of current industry data, conference proceedings, academic papers, and academic books on the subjects of petroleum refinery economics, refinery financing, refinery operations, and project finance generally and specifically in the oil and gas industry; evaluation of expert opinions from journal articles; working papers from international bodies like the World Bank and the International Energy Agency; and experience from playing an active role in the development and financing of US$ 10 Billion greenfield oil development project in Uganda. The paper also applies the discounted cash flow modelling to illustrate the circumstances of an inland greenfield refinery project in Uganda. Greenfield refinery and petrochemical projects are still necessary in sub-Saharan Africa to, among other aspirations, support the transition from traditional sources of energy like biomass to such modern forms as liquefied petroleum gas. Project developers and host governments will be required to structure projects that support global climate change goals without occasioning undue delays to project execution.

Keywords: financing, refinery and petrochemical economics, Africa, project finance

Procedia PDF Downloads 59
2881 Catchment Yield Prediction in an Ungauged Basin Using PyTOPKAPI

Authors: B. S. Fatoyinbo, D. Stretch, O. T. Amoo, D. Allopi

Abstract:

This study extends the use of the Drainage Area Regionalization (DAR) method in generating synthetic data and calibrating PyTOPKAPI stream yield for an ungauged basin at a daily time scale. The generation of runoff in determining a river yield has been subjected to various topographic and spatial meteorological variables, which integers form the Catchment Characteristics Model (CCM). Many of the conventional CCM models adapted in Africa have been challenged with a paucity of adequate, relevance and accurate data to parameterize and validate the potential. The purpose of generating synthetic flow is to test a hydrological model, which will not suffer from the impact of very low flows or very high flows, thus allowing to check whether the model is structurally sound enough or not. The employed physically-based, watershed-scale hydrologic model (PyTOPKAPI) was parameterized with GIS-pre-processing parameters and remote sensing hydro-meteorological variables. The validation with mean annual runoff ratio proposes a decent graphical understanding between observed and the simulated discharge. The Nash-Sutcliffe efficiency and coefficient of determination (R²) values of 0.704 and 0.739 proves strong model efficiency. Given the current climate variability impact, water planner can now assert a tool for flow quantification and sustainable planning purposes.

Keywords: catchment characteristics model, GIS, synthetic data, ungauged basin

Procedia PDF Downloads 327
2880 Microalgae Applied to the Reduction of Biowaste Produced by Fruit Fly Drosophila melanogaster

Authors: Shuang Qiu, Zhipeng Chen, Lingfeng Wang, Shijian Ge

Abstract:

Biowastes are a concern due to the large amounts of commercial food required for model animals during the biomedical research. Searching for sustainable food alternatives with negligible physiological effects on animals is critical to solving or reducing this challenge. Microalgae have been demonstrated as suitable for both human consumption and animal feed in addition to biofuel and bioenergy applications. In this study, the possibility of using Chlorella vulgaris and Senedesmus obliquus as a feed replacement to Drosophila melanogaster, one of the fly models commonly used in biomedical studies, was investigated to assess the fly locomotor activity, motor pattern, lifespan, and body weight. Compared to control, flies fed on 60% or 80% (w/w) microalgae exhibited varied walking performance including travel distance and apparent step size, and flies treated with 40% microalgae had shorter lifespans and decreased body weight. However, the 20% microalgae treatment showed no statistical differences in all parameters tested with respect to the control. When partially including 20% microalgae in the standard food, it can annually reduce the food waste (~ 202 kg) by 22.7 % and save $ 7,200 of the food cost, offering an environmentally superior and cost-effective food alternative without compromising physiological performance.

Keywords: animal feed, Chlorella vulgaris, Drosophila melanogaster, food waste, microalgae

Procedia PDF Downloads 166
2879 Optimization of a Convolutional Neural Network for the Automated Diagnosis of Melanoma

Authors: Kemka C. Ihemelandu, Chukwuemeka U. Ihemelandu

Abstract:

The incidence of melanoma has been increasing rapidly over the past two decades, making melanoma a current public health crisis. Unfortunately, even as screening efforts continue to expand in an effort to ameliorate the death rate from melanoma, there is a need to improve diagnostic accuracy to decrease misdiagnosis. Artificial intelligence (AI) a new frontier in patient care has the ability to improve the accuracy of melanoma diagnosis. Convolutional neural network (CNN) a form of deep neural network, most commonly applied to analyze visual imagery, has been shown to outperform the human brain in pattern recognition. However, there are noted limitations with the accuracy of the CNN models. Our aim in this study was the optimization of convolutional neural network algorithms for the automated diagnosis of melanoma. We hypothesized that Optimal selection of the momentum and batch hyperparameter increases model accuracy. Our most successful model developed during this study, showed that optimal selection of momentum of 0.25, batch size of 2, led to a superior performance and a faster model training time, with an accuracy of ~ 83% after nine hours of training. We did notice a lack of diversity in the dataset used, with a noted class imbalance favoring lighter vs. darker skin tone. Training set image transformations did not result in a superior model performance in our study.

Keywords: melanoma, convolutional neural network, momentum, batch hyperparameter

Procedia PDF Downloads 101
2878 Establishment of a Classifier Model for Early Prediction of Acute Delirium in Adult Intensive Care Unit Using Machine Learning

Authors: Pei Yi Lin

Abstract:

Objective: The objective of this study is to use machine learning methods to build an early prediction classifier model for acute delirium to improve the quality of medical care for intensive care patients. Background: Delirium is a common acute and sudden disturbance of consciousness in critically ill patients. After the occurrence, it is easy to prolong the length of hospital stay and increase medical costs and mortality. In 2021, the incidence of delirium in the intensive care unit of internal medicine was as high as 59.78%, which indirectly prolonged the average length of hospital stay by 8.28 days, and the mortality rate is about 2.22% in the past three years. Therefore, it is expected to build a delirium prediction classifier through big data analysis and machine learning methods to detect delirium early. Method: This study is a retrospective study, using the artificial intelligence big data database to extract the characteristic factors related to delirium in intensive care unit patients and let the machine learn. The study included patients aged over 20 years old who were admitted to the intensive care unit between May 1, 2022, and December 31, 2022, excluding GCS assessment <4 points, admission to ICU for less than 24 hours, and CAM-ICU evaluation. The CAMICU delirium assessment results every 8 hours within 30 days of hospitalization are regarded as an event, and the cumulative data from ICU admission to the prediction time point are extracted to predict the possibility of delirium occurring in the next 8 hours, and collect a total of 63,754 research case data, extract 12 feature selections to train the model, including age, sex, average ICU stay hours, visual and auditory abnormalities, RASS assessment score, APACHE-II Score score, number of invasive catheters indwelling, restraint and sedative and hypnotic drugs. Through feature data cleaning, processing and KNN interpolation method supplementation, a total of 54595 research case events were extracted to provide machine learning model analysis, using the research events from May 01 to November 30, 2022, as the model training data, 80% of which is the training set for model training, and 20% for the internal verification of the verification set, and then from December 01 to December 2022 The CU research event on the 31st is an external verification set data, and finally the model inference and performance evaluation are performed, and then the model has trained again by adjusting the model parameters. Results: In this study, XG Boost, Random Forest, Logistic Regression, and Decision Tree were used to analyze and compare four machine learning models. The average accuracy rate of internal verification was highest in Random Forest (AUC=0.86), and the average accuracy rate of external verification was in Random Forest and XG Boost was the highest, AUC was 0.86, and the average accuracy of cross-validation was the highest in Random Forest (ACC=0.77). Conclusion: Clinically, medical staff usually conduct CAM-ICU assessments at the bedside of critically ill patients in clinical practice, but there is a lack of machine learning classification methods to assist ICU patients in real-time assessment, resulting in the inability to provide more objective and continuous monitoring data to assist Clinical staff can more accurately identify and predict the occurrence of delirium in patients. It is hoped that the development and construction of predictive models through machine learning can predict delirium early and immediately, make clinical decisions at the best time, and cooperate with PADIS delirium care measures to provide individualized non-drug interventional care measures to maintain patient safety, and then Improve the quality of care.

Keywords: critically ill patients, machine learning methods, delirium prediction, classifier model

Procedia PDF Downloads 76
2877 A Stochastic Model to Predict Earthquake Ground Motion Duration Recorded in Soft Soils Based on Nonlinear Regression

Authors: Issam Aouari, Abdelmalek Abdelhamid

Abstract:

For seismologists, the characterization of seismic demand should include the amplitude and duration of strong shaking in the system. The duration of ground shaking is one of the key parameters in earthquake resistant design of structures. This paper proposes a nonlinear statistical model to estimate earthquake ground motion duration in soft soils using multiple seismicity indicators. Three definitions of ground motion duration proposed by literature have been applied. With a comparative study, we select the most significant definition to use for predict the duration. A stochastic model is presented for the McCann and Shah Method using nonlinear regression analysis based on a data set for moment magnitude, source to site distance and site conditions. The data set applied is taken from PEER strong motion databank and contains shallow earthquakes from different regions in the world; America, Turkey, London, China, Italy, Chili, Mexico...etc. Main emphasis is placed on soft site condition. The predictive relationship has been developed based on 600 records and three input indicators. Results have been compared with others published models. It has been found that the proposed model can predict earthquake ground motion duration in soft soils for different regions and sites conditions.

Keywords: duration, earthquake, prediction, regression, soft soil

Procedia PDF Downloads 153
2876 A Comprehensive Review of Adaptive Building Energy Management Systems Based on Users’ Feedback

Authors: P. Nafisi Poor, P. Javid

Abstract:

Over the past few years, the idea of adaptive buildings and specifically, adaptive building energy management systems (ABEMS) has become popular. Well-performed management in terms of energy is to create a balance between energy consumption and user comfort; therefore, in new energy management models, efficient energy consumption is not the sole factor and the user's comfortability is also considered in the calculations. One of the main ways of measuring this factor is by analyzing user feedback on the conditions to understand whether they are satisfied with conditions or not. This paper provides a comprehensive review of recent approaches towards energy management systems based on users' feedbacks and subsequently performs a comparison between them premised upon their efficiency and accuracy to understand which approaches were more accurate and which ones resulted in a more efficient way of minimizing energy consumption while maintaining users' comfortability. It was concluded that the highest accuracy rate among the presented works was 95% accuracy in determining satisfaction and up to 51.08% energy savings can be achieved without disturbing user’s comfort. Considering the growing interest in designing and developing adaptive buildings, these studies can support diverse inquiries about this subject and can be used as a resource to support studies and researches towards efficient energy consumption while maintaining the comfortability of users.

Keywords: adaptive buildings, energy efficiency, intelligent buildings, user comfortability

Procedia PDF Downloads 133
2875 Methodology of Preliminary Design and Performance of a Axial-Flow Fan through CFD

Authors: Ramiro Gustavo Ramirez Camacho, Waldir De Oliveira, Eraldo Cruz Dos Santos, Edna Raimunda Da Silva, Tania Marie Arispe Angulo, Carlos Eduardo Alves Da Costa, Tânia Cristina Alves Dos Reis

Abstract:

It presents a preliminary design methodology of an axial fan based on the lift wing theory and the potential vortex hypothesis. The literature considers a study of acoustic and engineering expertise to model a fan with low noise. Axial fans with inadequate intake geometry, often suffer poor condition of the flow at the entrance, varying from velocity profiles spatially asymmetric to swirl floating with respect to time, this produces random forces acting on the blades. This produces broadband gust noise which in most cases triggers the tonal noise. The analysis of the axial flow fan will be conducted for the solution of the Navier-Stokes equations and models of turbulence in steady and transitory (RANS - URANS) 3-D, in order to find an efficient aerodynamic design, with low noise and suitable for industrial installation. Therefore, the process will require the use of computational optimization methods, aerodynamic design methodologies, and numerical methods as CFD- Computational Fluid Dynamics. The objective is the development of the methodology of the construction axial fan, provide of design the geometry of the blade, and evaluate aerodynamic performance

Keywords: Axial fan design, CFD, Preliminary Design, Optimization

Procedia PDF Downloads 396
2874 A Simple Computational Method for the Gravitational and Seismic Soil-Structure-Interaction between New and Existent Buildings Sites

Authors: Nicolae Daniel Stoica, Ion Mierlus Mazilu

Abstract:

This work is one of numerical research and aims to address the issue of the design of new buildings in a 3D location of existing buildings. In today's continuous development and congestion of urban centers is a big question about the influence of the new buildings on an already existent vicinity site. Thus, in this study, we tried to focus on how existent buildings may be affected by any newly constructed buildings and in how far this influence is really decreased. The problem of modeling the influence of interaction between buildings is not simple in any area in the world, and neither in Romania. Unfortunately, most often the designers not done calculations that can determine how close to reality these 3D influences nor the simplified method and the more superior methods. In the most literature making a "shield" (the pilots or molded walls) is absolutely sufficient to stop the influence between the buildings, and so often the soil under the structure is ignored in the calculation models. The main causes for which the soil is neglected in the analysis are related to the complexity modeling of interaction between soil and structure. In this paper, based on a new simple but efficient methodology we tried to determine for a lot of study cases the influence, in terms of assessing the interaction land structure on the behavior of structures that influence a new building on an existing one. The study covers additional subsidence that may occur during the execution of new works and after its completion. It also highlighted the efforts diagrams and deflections in the soil for both the original case and the final stage. This is necessary to see to what extent the expected impact of the new building on existing areas.

Keywords: soil, structure, interaction, piles, earthquakes

Procedia PDF Downloads 291
2873 Thermoelectric Blanket for Aiding the Treatment of Cerebral Hypoxia and Other Related Conditions

Authors: Sarayu Vanga, Jorge Galeano-Cabral, Kaya Wei

Abstract:

Cerebral hypoxia refers to a condition in which there is a decrease in oxygen supply to the brain. Patients suffering from this condition experience a decrease in their body temperature. While there isn't any cure to treat cerebral hypoxia as of date, certain procedures are utilized to help aid in the treatment of the condition. Regulating the body temperature is an example of one of those procedures. Hypoxia is well known to reduce the body temperature of mammals, although the neural origins of this response remain uncertain. In order to speed recovery from this condition, it is necessary to maintain a stable body temperature. In this study, we present an approach to regulating body temperature for patients who suffer from cerebral hypoxia or other similar conditions. After a thorough literature study, we propose the use of thermoelectric blankets, which are temperature-controlled thermal blankets based on thermoelectric devices. These blankets are capable of heating up and cooling down the patient to stabilize body temperature. This feature is possible through the reversible effect that thermoelectric devices offer while behaving as a thermal sensor, and it is an effective way to stabilize temperature. Thermoelectricity is the direct conversion of thermal to electrical energy and vice versa. This effect is now known as the Seebeck effect, and it is characterized by the Seebeck coefficient. In such a configuration, the device has cooling and heating sides with temperatures that can be interchanged by simply switching the direction of the current input in the system. This design integrates various aspects, including a humidifier, ventilation machine, IV-administered medication, air conditioning, circulation device, and a body temperature regulation system. The proposed design includes thermocouples that will trigger the blanket to increase or decrease a set temperature through a medical temperature sensor. Additionally, the proposed design allows an efficient way to control fluctuations in body temperature while being cost-friendly, with an expected cost of 150 dollars. We are currently working on developing a prototype of the design to collect thermal and electrical data under different conditions and also intend to perform an optimization analysis to improve the design even further. While this proposal was developed for treating cerebral hypoxia, it can also aid in the treatment of other related conditions, as fluctuations in body temperature appear to be a common symptom that patients have for many illnesses.

Keywords: body temperature regulation, cerebral hypoxia, thermoelectric, blanket design

Procedia PDF Downloads 160
2872 Research on Resilience-Oriented Disintegration in System-of-System

Authors: Hang Yang, Jiahao Liu, Jichao Li, Kewei Yang, Minghao Li, Bingfeng Ge

Abstract:

The system-of-systems (SoS) are utilized to characterize networks formed by integrating individual complex systems that demonstrate interdependence and interconnectedness. Research on the disintegration issue in SoS is significant in improving network survivability, maintaining network security, and optimizing SoS architecture. Accordingly, this study proposes an integrated framework called resilience-oriented disintegration in SoS (SoSRD), for modeling and solving the issue of SoS disintegration. Firstly, a SoS disintegration index (SoSDI) is presented to evaluate the disintegration effect of SoS. This index provides a practical description of the disintegration process and is the first integration of the network disintegration model and resilience models. Subsequently, we propose a resilience-oriented disintegration method based on reinforcement learning (RDRL) to enhance the efficiency of SoS disintegration. This method is not restricted by the problem scenario as well as considering the coexistence of disintegration (node/link removal) and recovery (node/link addition) during the process of SoS disintegration. Finally, the effectiveness and superiority of the proposed SoSRD are demonstrated through a case study. We demonstrate that our proposed framework outperforms existing indexes and methods in both node and link disintegration scenarios, providing a fresh perspective on network disintegration. The findings provide crucial insights into dismantling harmful SoS and designing a more resilient SoS.

Keywords: system-of-systems, disintegration index, resilience, reinforcement learning

Procedia PDF Downloads 14
2871 Application of Neutron-Gamma Technologies for Soil Elemental Content Determination and Mapping

Authors: G. Yakubova, A. Kavetskiy, S. A. Prior, H. A. Torbert

Abstract:

In-situ soil carbon determination over large soil surface areas (several hectares) is required in regard to carbon sequestration and carbon credit issues. This capability is important for optimizing modern agricultural practices and enhancing soil science knowledge. Collecting and processing representative field soil cores for traditional laboratory chemical analysis is labor-intensive and time-consuming. The neutron-stimulated gamma analysis method can be used for in-situ measurements of primary elements in agricultural soils (e.g., Si, Al, O, C, Fe, and H). This non-destructive method can assess several elements in large soil volumes with no need for sample preparation. Neutron-gamma soil elemental analysis utilizes gamma rays issued from different neutron-nuclei interactions. This process has become possible due to the availability of commercial portable pulse neutron generators, high-efficiency gamma detectors, reliable electronics, and measurement/data processing software complimented by advances in state-of-the-art nuclear physics methods. In Pulsed Fast Thermal Neutron Analysis (PFTNA), soil irradiation is accomplished using a pulsed neutron flux, and gamma spectra acquisition occurs both during and between pulses. This method allows the inelastic neutron scattering (INS) gamma spectrum to be separated from the thermal neutron capture (TNC) spectrum. Based on PFTNA, a mobile system for field-scale soil elemental determinations (primarily carbon) was developed and constructed. Our scanning methodology acquires data that can be directly used for creating soil elemental distribution maps (based on ArcGIS software) in a reasonable timeframe (~20-30 hectares per working day). Created maps are suitable for both agricultural purposes and carbon sequestration estimates. The measurement system design, spectra acquisition process, strategy for acquiring field-scale carbon content data, and mapping of agricultural fields will be discussed.

Keywords: neutron gamma analysis, soil elemental content, carbon sequestration, carbon credit, soil gamma spectroscopy, portable neutron generators, ArcMap mapping

Procedia PDF Downloads 90
2870 Effective Validation Model and Use of Mobile-Health Apps for Elderly People

Authors: Leonardo Ramirez Lopez, Edward Guillen Pinto, Carlos Ramos Linares

Abstract:

The controversy brought about by the increasing use of mHealth apps and their effectiveness for disease prevention and diagnosis calls for immediate control. Although a critical topic in research areas such as medicine, engineering, economics, among others, this issue lacks reliable implementation models. However, projects such as Open Web Application Security Project (OWASP) and various studies have helped to create useful and reliable apps. This research is conducted under a quality model to optimize two mHealth apps for older adults. Results analysis on the use of two physical activity monitoring apps - AcTiv (physical activity) and SMCa (energy expenditure) - is positive and ideal. Through a theoretical and practical analysis, precision calculations and personal information control of older adults for disease prevention and diagnosis were performed. Finally, apps are validated by a physician and, as a result, they may be used as health monitoring tools in physical performance centers or any other physical activity. The results obtained provide an effective validation model for this type of mobile apps, which, in turn, may be applied by other software developers that along with medical staff would offer digital healthcare tools for elderly people.

Keywords: model, validation, effective, healthcare, elderly people, mobile app

Procedia PDF Downloads 218
2869 Negotiating Autonomy in Women’s Political Participation: The Case of Elected Women’s Representatives from Jharkhand

Authors: Rajeshwari Balasubramanian, Margit Van Wessel, Nandini Deo

Abstract:

The participation of women in local bodies witnessed a rise after the implementation of 73rd and 74th Amendments to the Indian Constitution which created quotas for women representatives. However, even when participation increased, it did not translate into meaningful contributions by women in local bodies. This led some civil society organisations (CSOs) to begin working with women panchayat representatives in various states to build their capacity for political participation. The focus of this paper is to study capacity building training by CSOs in Jharkhand. The paper maps how the training helps women elected representatives to negotiate their autonomy at multiple levels. The paper describes the capacity building program conducted by an international feminist organisation along with its seven local partners in Jharkhand. The central question that the study asks is: How does capacity building training by CSOs in Jharkhand impact the autonomy of elected women representatives? It uses a qualitative research methodology based on empirical data gathered through field visits in four districts of Jharkhand (Chatra, Hazaribagh, East Singhbum and Ranchi) where the program was implemented for three years. The study found that women elected representatives had to develop strategies to negotiate their choice to move out of their homes and attend the training conducted by CSOs. The ability to participate in the training programs itself was a significant achievement of personal autonomy for many women. The training provided them a platform to voice their opinion and appreciate their own value as panchayat leaders. This realization allowed them to negotiate their presence and a space for themselves in Gram panchayats. A Foucauldian approach to analyze capacity building workshops might lead us to see them as systems in which CSOs impose a form of governmentality on rural elected representatives. Instead, what we see here is a much more complex negotiation of agency in which the CSO creates spaces and practices that allow women to achieve their own forms of autonomy. The study concludes that the impact of the training on the autonomy of these women is based on their everyday negotiations of time, space and mobility. Autonomy for these elected women representatives is also contextual and relative, as they seem to realize it during the training process. The training allows the women to not only negotiate their participation in panchayats but also challenge everyday practices that are rooted in patriarchy.

Keywords: autonomy, feminist organization, local bodies, political participation

Procedia PDF Downloads 149
2868 The Asymmetric Proximal Support Vector Machine Based on Multitask Learning for Classification

Authors: Qing Wu, Fei-Yan Li, Heng-Chang Zhang

Abstract:

Multitask learning support vector machines (SVMs) have recently attracted increasing research attention. Given several related tasks, the single-task learning methods trains each task separately and ignore the inner cross-relationship among tasks. However, multitask learning can capture the correlation information among tasks and achieve better performance by training all tasks simultaneously. In addition, the asymmetric squared loss function can better improve the generalization ability of the models on the most asymmetric distributed data. In this paper, we first make two assumptions on the relatedness among tasks and propose two multitask learning proximal support vector machine algorithms, named MTL-a-PSVM and EMTL-a-PSVM, respectively. MTL-a-PSVM seeks a trade-off between the maximum expectile distance for each task model and the closeness of each task model to the general model. As an extension of the MTL-a-PSVM, EMTL-a-PSVM can select appropriate kernel functions for shared information and private information. Besides, two corresponding special cases named MTL-PSVM and EMTLPSVM are proposed by analyzing the asymmetric squared loss function, which can be easily implemented by solving linear systems. Experimental analysis of three classification datasets demonstrates the effectiveness and superiority of our proposed multitask learning algorithms.

Keywords: multitask learning, asymmetric squared loss, EMTL-a-PSVM, classification

Procedia PDF Downloads 134
2867 Developing the Involvement of Nurses in Determining Health Policies

Authors: Yafa Haron, Hanna Adami

Abstract:

Background: World Health Organization emphasizes the contribution of nurses in planning and implementing health policies and reforms. Aim: To evaluate nursing students’ attitudes towards nurses’ involvement in health policy issues. Methods: Mixed-methods; qualitative and quantitative – a descriptive study. Participants - nursing students who were enrolled in their last year in the undergraduate program (BSN). Qualitative data included two open-ended questions: What is health policy and what is the importance of studying health policy, and 18 statements on the Likert Scale range 1-5. Results: Qualitativeanalysisrevealed that the majority of students defined health policy as a set of rules and regulations that defined procedures, borders, and proper conduct. 73% of students responded that nurses should be active in policymaking, but only 22% thought that nurses were currently involved in political issues. 28% thought that nurses do not have the knowledge and the time needed (60%) for political activity. 77% thought that the work environment did not encourage nurses to be politically active. Nursing students are aware of the importance towards nurses’ involvement in health policy issues, however, they do not have role models based on their low evaluation regarding nurses’ involvement in the health policy decision making process at the local or national level. Conclusions: Results emphasize the importance and the need of implementation the recommendation to include “advance policy changes” as core competency in nursing education and practice.

Keywords: health policy, nursing education, health systems, student perceptions

Procedia PDF Downloads 97
2866 Assessment and Prediction of Vehicular Emissions in Commonwealth Avenue, Quezon City at Various Policy and Technology Scenarios Using Simple Interactive Model (SIM-Air)

Authors: Ria M. Caramoan, Analiza P. Rollon, Karl N. Vergel

Abstract:

The Simple Interactive Models for Better Air Quality (SIM-air) is an integrated approach model that allows the available information to support the integrated urban air quality management. This study utilized the vehicular air pollution information system module of SIM-air for the assessment of vehicular emissions in Commonwealth Avenue, Quezon City, Philippines. The main objective of the study is to assess and predict the contribution of different types of vehicles to the vehicular emissions in terms of PM₁₀, SOₓ, and NOₓ at different policy and technology scenarios. For the base year 2017, the results show vehicular emissions of 735.46 tons of PM₁₀, 108.90 tons of SOₓ, and 2,101.11 tons of NOₓ. Motorcycle is the major source of particulates contributing about 52% of the PM₁₀ emissions. Meanwhile, Public Utility Jeepneys contribute 27% of SOₓ emissions and private cars using gasoline contribute 39% of NOₓ emissions. Ambient air quality monitoring was also conducted in the study area for the standard parameters of PM₁₀, S0₂, and NO₂. Results show an average of 88.11 µg/Ncm, 47.41 µg/Ncm and 22.54 µg/Ncm for PM₁₀, N0₂, and SO₂, respectively, all were within the DENR National Ambient Air Quality Guideline Values. Future emissions of PM₁₀, NOₓ, and SOₓ are estimated at different scenarios. Results show that in the year 2030, PM₁₀ emissions will be increased by 186.2%. NOₓ emissions and SOₓ emissions will also be increased by 38.9% and 5.5%, without the implementation of the scenarios.

Keywords: ambient air quality, emissions inventory, mobile air pollution, vehicular emissions

Procedia PDF Downloads 137
2865 Creative Peace Diplomacy Model by the Perspective of Dialogue Management for International Relations

Authors: Bilgehan Gültekin, Tuba Gültekin

Abstract:

Peace diplomacy is the most important international tool to keep peace all over the world. The study titled “peace diplomacy for international relations” is consist of three part. In the first part, peace diplomacy is going to be introduced as a tool of peace communication and peace management. And, in this part, peace communication will be explained by international communication perspective. In the second part of the study,public relations events and communication campaigns will be developed originally for peace diplomacy. In this part, it is aimed original public communication dialogue management tools for peace diplomacy. the aim of the final part of the study, is to produce original public communication model for international relations. The model includes peace modules, peace management projects, original dialogue procedures and protocols, dialogue education, dialogue management strategies, peace actors, communication models, peace team management and public diplomacy steps. The creative part of the study aims to develop a model used for international relations for all countries. Creative Peace Diplomacy Model will be developed in the case of Turkey-Turkey-France and Turkey-Greece relations. So, communication and public relations events and campaigns are going to be developed as original for only this study.

Keywords: peace diplomacy, public communication model, dialogue management, international relations

Procedia PDF Downloads 541
2864 Anomaly Detection in a Data Center with a Reconstruction Method Using a Multi-Autoencoders Model

Authors: Victor Breux, Jérôme Boutet, Alain Goret, Viviane Cattin

Abstract:

Early detection of anomalies in data centers is important to reduce downtimes and the costs of periodic maintenance. However, there is little research on this topic and even fewer on the fusion of sensor data for the detection of abnormal events. The goal of this paper is to propose a method for anomaly detection in data centers by combining sensor data (temperature, humidity, power) and deep learning models. The model described in the paper uses one autoencoder per sensor to reconstruct the inputs. The auto-encoders contain Long-Short Term Memory (LSTM) layers and are trained using the normal samples of the relevant sensors selected by correlation analysis. The difference signal between the input and its reconstruction is then used to classify the samples using feature extraction and a random forest classifier. The data measured by the sensors of a data center between January 2019 and May 2020 are used to train the model, while the data between June 2020 and May 2021 are used to assess it. Performances of the model are assessed a posteriori through F1-score by comparing detected anomalies with the data center’s history. The proposed model outperforms the state-of-the-art reconstruction method, which uses only one autoencoder taking multivariate sequences and detects an anomaly with a threshold on the reconstruction error, with an F1-score of 83.60% compared to 24.16%.

Keywords: anomaly detection, autoencoder, data centers, deep learning

Procedia PDF Downloads 194
2863 Offloading Knowledge-Keeping to Digital Technology and the Attrition of Socio-Cultural Life

Authors: Sophia Melanson Ricciardone

Abstract:

Common vexations concerning the impact of contemporary media technology on our daily lives tend to conjure mental representations of digital specters that surreptitiously invade the privacy of our most intimate spaces. While legitimacy assuredly sustains these concerns, examining them in isolation from other attributable phenomena to the problems created by our hyper-mediated conditions does not supply a complete account of the deleterious cost of integrating digital affordances into the banal cadence of our shared socio-cultural realities. As we continue to subconsciously delegate facets of our social and cognitive lives to digital technology, the very faculties that have enabled our species to thrive and invent technology in the first place are at risk of attrition – namely our capacity to sustain attention while synthesizing information in working memory to produce creative and inventive constructions for our shared social existence. Though the offloading of knowledge-keeping to fellow social agents belonging to our family and community circles is an enduring intuitive phenomenon across human societies – what social psychologists refer to as transactive memory – in offloading our various socio-cognitive faculties to digital technology, we may plausibly be supplanting the visceral social connections forged by transactive memory. This paper will present related research and literature produced across the disciplines of sociobiology, socio-cultural anthropology, social psychology, cognitive semiotics and communication and media studies that directly and indirectly address the social precarity cultivated by digital technologies. This body of scholarly work will then be situated within common areas of interest belonging to digital anthropology, including the groundbreaking work of Pavel Curtis, Christopher Kelty, Lynn Cherny, Vincent Duclos, Nick Seaver, and Sherry Turkle. It is anticipated that in harmonizing these overlapping areas of intradisciplinary interest, this paper can weave together the disparate connections across spheres of knowledge that help delineate the conditions of our contemporary digital existence.

Keywords: cognition, digital media, knowledge keeping, transactive memory

Procedia PDF Downloads 139
2862 The Role of Strategic Metals in Cr-Al-Pt-V Composition of Protective Bond Coats

Authors: A. M. Pashayev, A. S. Samedov, T. B. Usubaliyev, N. Sh. Yusifov

Abstract:

Different types of coating technologies are widely used for gas turbine blades. Thermal barrier coatings, consisting of ceramic top coat, thermally grown oxide and a metallic bond coat are used in applications for thermal protection of hot section components in gas turbine engines. Operational characteristics and longevity of high-temperature turbine blades substantially depend on a right choice of composition of the protective thermal barrier coatings. At a choice of composition of a coating and content of the basic elements it is necessary to consider following factors, as minimum distinctions of coefficients of thermal expansions of elements, level of working temperatures and composition of the oxidizing environment, defining the conditions for the formation of protective layers, intensity of diffusive processes and degradation speed of protective properties of elements, extent of influence on the fatigue durability of details during operation, using of elements with high characteristics of thermal stability and satisfactory resilience of gas corrosion, density, hardness, thermal conduction and other physical characteristics. Forecasting and a choice of a thermal barrier coating composition, all above factors at the same time cannot be considered, as some of these characteristics are defined by experimental studies. The implemented studies and investigations show that one of the main failures of coatings used on gas turbine blades is related to not fully taking the physical-chemical features of elements into consideration during the determination of the composition of alloys. It leads to the formation of more difficult spatial structure, composition which also changes chaotically in some interval of concentration that doesn't promote thermal and structural firmness of a coating. For the purpose of increasing the thermal and structural resistant of gas turbine blade coatings is offered a new approach to forecasting of composition on the basis of analysis of physical-chemical characteristics of alloys taking into account the size factor, electron configuration, type of crystal lattices and Darken-Gurry method. As a result, of calculations and experimental investigations is offered the new four-component metallic bond coat on the basis of chrome for the gas turbine blades.

Keywords: gas turbine blades, thermal barrier coating, metallic bond coat, strategic metals, physical-chemical features

Procedia PDF Downloads 315
2861 The Experimental and Numerical Analysis of the Joining Processes for Air Conditioning Systems

Authors: M.St. Węglowski, D. Miara, S. Błacha, J. Dworak, J. Rykała, K. Kwieciński, J. Pikuła, G. Ziobro, A. Szafron, P. Zimierska-Nowak, M. Richert, P. Noga

Abstract:

In the paper the results of welding of car’s air-conditioning elements are presented. These systems based on, mainly, the environmental unfriendly refrigerants. Thus, the producers of cars will have to stop using traditional refrigerant and to change it to carbon dioxide (R744). This refrigerant is environmental friendly. However, it should be noted that the air condition system working with R744 refrigerant operates at high temperature (up to 150 °C) and high pressure (up to 130 bar). These two parameters are much higher than for other refrigerants. Thus new materials, design as well as joining technologies are strongly needed for these systems. AISI 304 and 316L steels as well as aluminium alloys 5xxx are ranked among the prospective materials. As a joining process laser welding, plasma welding, electron beam welding as well as high rotary friction welding can be applied. In the study, the metallographic examination based on light microscopy as well as SEM was applied to estimate the quality of welded joints. The analysis of welding was supported by numerical modelling based on Sysweld software. The results indicated that using laser, plasma and electron beam welding, it is possible to obtain proper quality of welds in stainless steel. Moreover, high rotary friction welding allows to guarantee the metallic continuity in the aluminium welded area. The metallographic examination revealed that the grain growth in the heat affected zone (HAZ) in laser and electron beam welded joints were not observed. It is due to low heat input and short welding time. The grain growth and subgrains can be observed at room temperature when the solidification mode is austenitic. This caused low microstructural changes during solidification. The columnar grain structure was found in the weld metal. Meanwhile, the equiaxed grains were detected in the interface. The numerical modelling of laser welding process allowed to estimate the temperature profile in the welded joint as well as predicts the dimensions of welds. The agreement between FEM analysis and experimental data was achieved.  

Keywords: car’s air–conditioning, microstructure, numerical modelling, welding

Procedia PDF Downloads 408
2860 Strengthening Evaluation of Steel Girder Bridge under Load Rating Analysis: Case Study

Authors: Qudama Albu-Jasim, Majdi Kanaan

Abstract:

A case study about the load rating and strengthening evaluation of the six-span of steel girders bridge in Colton city of State of California is investigated. To simulate the load rating strengthening assessment for the Colton Overhead bridge, a three-dimensional finite element model built in the CSiBridge program is simulated. Three-dimensional finite-element models of the bridge are established considering the nonlinear behavior of critical bridge components to determine the feasibility and strengthening capacity under load rating analysis. The bridge was evaluated according to Caltrans Bridge Load Rating Manual 1st edition for rating the superstructure using the Load and Resistance Factor Rating (LRFR) method. The analysis for the bridge was based on load rating to determine the largest loads that can be safely placed on existing I-girder steel members and permitted to pass over the bridge. Through extensive numerical simulations, the bridge is identified to be deficient in flexural and shear capacities, and therefore strengthening for reducing the risk is needed. An in-depth parametric study is considered to evaluate the sensitivity of the bridge’s load rating response to variations in its structural parameters. The parametric analysis has exhibited that uncertainties associated with the steel’s yield strength, the superstructure’s weight, and the diaphragm configurations should be considered during the fragility analysis of the bridge system.

Keywords: load rating, CSIBridge, strengthening, uncertainties, case study

Procedia PDF Downloads 211
2859 Jan’s Life-History: Changing Faces of Managerial Masculinities and Consequences for Health

Authors: Susanne Gustafsson

Abstract:

Life-history research is an extraordinarily fruitful method to use for social analysis and gendered health analysis in particular. Its potential is illustrated through a case study drawn from a Swedish project. It reveals an old type of masculinity that faces difficulties when carrying out two sets of demands simultaneously, as a worker/manager and as a father/husband. The paper illuminates the historical transformation of masculinity and the consequences of this for health. We draw on the idea of the “changing faces of masculinity” to explore the dynamism and complexity of gendered health. An empirical case is used for its illustrative abilities. Jan, a middle-level manager and father employed in the energy sector in urban Sweden is the subject of this paper. Jan’s story is one of 32 semi-structured interviews included in an extended study focusing on well-being at work. The results reveal a face of masculinity conceived of in middle-level management as tacitly linked to the neoliberal doctrine. Over a couple of decades, the idea of “flexibility” was turned into a valuable characteristic that everyone was supposed to strive for. This resulted in increased workloads. Quite a few employees, and managers, in particular, find themselves working both day and night. This may explain why not having enough time to spend with children and family members is a recurring theme in the data. Can this way of doing be linked to masculinity and health? The first author’s research has revealed that the use of gender in health science is not sufficiently or critically questioned. This lack of critical questioning is a serious problem, especially since ways of doing gender affect health. We suggest that gender reproduction and gender transformation are interconnected, regardless of how they affect health. They are recognized as two sides of the same phenomenon, and minor movements in one direction or the other become crucial for understanding its relation to health. More or less, at the same time, as Jan’s masculinity was reproduced in response to workplace practices, Jan’s family position was transformed—not totally but by a degree or two, and these degrees became significant for the family’s health and well-being. By moving back and forth between varied events in Jan’s biographical history and his sociohistorical life span, it becomes possible to show that in a time of gender transformations, power relations can be renegotiated, leading to consequences for health.

Keywords: changing faces of masculinity, gendered health, life-history research method, subverter

Procedia PDF Downloads 113
2858 Library Outreach After COVID: Making the Case for In-Person Library Visits

Authors: Lucas Berrini

Abstract:

Academic libraries have always struggled with engaging with students and faculty. Striking the balance between what the community needs and what the library can afford has also been a point of contention for libraries. As academia begins to return to a new normal after COVID, library staff are rethinking how remind patrons that the library is open and ready for business. NC Wesleyan, a small liberal arts school in eastern North Carolina, decided to be proactive and reach out to the academic community. After shutting down in 2020 for COVID, the campus library saw a marked decrease in in-person attendance. For a small school whose operational budget was tied directly to tuition payments, it was imperative for the library to remind faculty and staff that they were open for business. At the beginning of the Summer 2022 term and continuing into the fall, the reference team created a marketing plan using email, physical meetings, and virtual events targeted at students and faculty as well as community members who utilized the facilities prior to COVID. The email blasts were gentle reminders that the building was open and available for use The target audiences were the community at large. Several of the emails contained reminders of previous events in the library that were student centered. The next phase of the email campaign centers on reminding the community about the libraries physical and electronic resources, including the makerspace lab. Language will indicate that student voices are needed, and a QR code is included for students to leave feedback as to what they want to see in the library. The final phase of the email blasts were faculty focused and invited them to connect with library reference staff for an in-person consultation on their research needs. While this phase is ongoing, the response has been positive, and staff are compiling data in hopes of working with administration to implement some of the requested services and materials. These email blasts will be followed up by in-person meetings with faculty and students who responded to the QR codes. This research is ongoing. This type of targeted outreach is new for Wesleyan. It is the hope of the library that by the end of Fall 2022, there will be a plan in place to address the needs and concerns of the students and faculty. Furthermore, the staff hopes to create a new sense of community for the students and staff of the university.

Keywords: academic, education, libraries, outreach

Procedia PDF Downloads 94
2857 A Literature Review and a Proposed Conceptual Framework for Learning Activities in Business Process Management

Authors: Carin Lindskog

Abstract:

Introduction: Long-term success requires an organizational balance between continuity (exploitation) and change (exploration). The problem of balancing exploitation and exploration is a common issue in studies of organizational learning. In order to better face the tough competition in the face of changes, organizations need to exploit their current business and explore new business fields by developing new capabilities. The purpose of this work in progress is to develop a conceptual framework to shed light on the relevance of 'learning activities', i.e., exploitation and exploration, on different levels. The research questions that will be addressed are as follows: What sort of learning activities are found in the Business Process Management (BPM) field? How can these activities be linked to the individual level, group, level, and organizational level? In the work, a literature review will first be conducted. This review will explore the status of learning activities in the BPM field. An outcome from the literature review will be a conceptual framework of learning activities based on the included publications. The learning activities will be categorized to focus on the categories exploitation, exploration or both and into the levels of individual, group, and organization. The proposed conceptual framework will be a valuable tool for analyzing the research field as well as identification of future research directions. Related Work: BPM has increased in popularity as a way of working to strengthen the quality of the work and meet the demands of efficiency. Due to the increase in BPM popularity, more and more organizations reporting on BPM failure. One reason for this is the lack of knowledge about the extended scope of BPM to other business contexts that include, for example, more creative business fields. Yet another reason for the failures are the fact of the employees’ are resistant to changes. The learning process in an organization is an ongoing cycle of reflection and action and is a process that can be initiated, developed and practiced. Furthermore, organizational learning is multilevel; therefore the theory of organizational learning needs to consider the individual, the group, and the organization level. Learning happens over time and across levels, but it also creates a tension between incorporating new learning (feed-forward) and exploiting or using what has already been learned (feedback). Through feed-forward processes, new ideas and actions move from the individual to the group to the organization level. At the same time, what has already been learned feeds back from the organization to a group to an individual and has an impact on how people act and think.

Keywords: business process management, exploitation, exploration, learning activities

Procedia PDF Downloads 124
2856 Mass Polarization in Three-Body System with Two Identical Particles

Authors: Igor Filikhin, Vladimir M. Suslov, Roman Ya. Kezerashvili, Branislav Vlahivic

Abstract:

The mass-polarization term of the three-body kinetic energy operator is evaluated for different systems which include two identical particles: A+A+B. The term has to be taken into account for the analysis of AB- and AA-interactions based on experimental data for two- and three-body ground state energies. In this study, we present three-body calculations within the framework of a potential model for the kaonic clusters K−K−p and ppK−, nucleus 3H and hypernucleus 6 ΛΛHe. The systems are well clustering as A+ (A+B) with a ground state energy E2 for the pair A+B. The calculations are performed using the method of the Faddeev equations in configuration space. The phenomenological pair potentials were used. We show a correlation between the mass ratio mA/mB and the value δB of the mass-polarization term. For bosonic-like systems, this value is defined as δB = 2E2 − E3, where E3 is three-body energy when VAA = 0. For the systems including three particles with spin(isospin), the models with average AB-potentials are used. In this case, the Faddeev equations become a scalar one like for the bosonic-like system αΛΛ. We show that the additional energy conected with the mass-polarization term can be decomposite to a sum of the two parts: exchenge related and reduced mass related. The state of the system can be described as the following: the particle A1 is bound within the A + B pair with the energy E2, and the second particle A2 is bound with the pair with the energy E3 − E2. Due to the identity of A particles, the particles A1 and A2 are interchangeable in the pair A + B. We shown that the mass polarization δB correlates with a type of AB potential using the system αΛΛ as an example.

Keywords: three-body systems, mass polarization, Faddeev equations, nuclear interactions

Procedia PDF Downloads 377
2855 A Literature Review Evaluating the Use of Online Problem-Based Learning and Case-Based Learning Within Dental Education

Authors: Thomas Turner

Abstract:

Due to the Covid-19 pandemic alternative ways of delivering dental education were required. As a result, many institutions moved teaching online. The impact of this is poorly understood. Is online problem-based learning (PBL) and case-based learning (CBL) effective and is it suitable in the post-pandemic era? PBL and CBL are both types of interactive, group-based learning which are growing in popularity within many dental schools. PBL was first introduced in the 1960’s and can be defined as learning which occurs from collaborative work to resolve a problem. Whereas CBL encourages learning from clinical cases, encourages application of knowledge and helps prepare learners for clinical practice. To evaluate the use of online PBL and CBL. A literature search was conducted using the CINAHL, Embase, PubMed and Web of Science databases. Literature was also identified from reference lists. Studies were only included from dental education. Seven suitable studies were identified. One of the studies found a high learner and facilitator satisfaction rate with online CBL. Interestingly one study found learners preferred CBL over PBL within an online format. A study also found, that within the context of distance learning, learners preferred a hybrid curriculum including PBL over a traditional approach. A further study pointed to the limitations of PBL within an online format, such as reduced interaction, potentially hindering the development of communication skills and the increased time and technology support required. An audience response system was also developed for use within CBL and had a high satisfaction rate. Interestingly one study found achievement of learning outcomes was correlated with the number of student and staff inputs within an online format. Whereas another study found the quantity of learner interactions were important to group performance, however the quantity of facilitator interactions was not. This review identified generally favourable evidence for the benefits of online PBL and CBL. However, there is limited high quality evidence evaluating these teaching methods within dental education and there appears to be limited evidence comparing online and faceto-face versions of these sessions. The importance of the quantity of learner interactions is evident, however the importance of the quantity of facilitator interactions appears to be questionable. An element to this may be down to the quality of interactions, rather than just quantity. Limitations of online learning regarding technological issues and time required for a session are also highlighted, however as learners and facilitators get familiar with online formats, these may become less of an issue. It is also important learners are encouraged to interact and communicate during these sessions, to allow for the development of communication skills. Interestingly CBL appeared to be preferred to PBL in an online format. This may reflect the simpler nature of CBL, however further research is required to explore this finding. Online CBL and PBL appear promising, however further research is required before online formats of these sessions are widely adopted in the post-pandemic era.

Keywords: case-based learning, online, problem-based learning, remote, virtual

Procedia PDF Downloads 77
2854 Application of GA Optimization in Analysis of Variable Stiffness Composites

Authors: Nasim Fallahi, Erasmo Carrera, Alfonso Pagani

Abstract:

Variable angle tow describes the fibres which are curvilinearly steered in a composite lamina. Significantly, stiffness tailoring freedom of VAT composite laminate can be enlarged and enabled. Composite structures with curvilinear fibres have been shown to improve the buckling load carrying capability in contrast with the straight laminate composites. However, the optimal design and analysis of VAT are faced with high computational efforts due to the increasing number of variables. In this article, an efficient optimum solution has been used in combination with 1D Carrera’s Unified Formulation (CUF) to investigate the optimum fibre orientation angles for buckling analysis. The particular emphasis is on the LE-based CUF models, which provide a Lagrange Expansions to address a layerwise description of the problem unknowns. The first critical buckling load has been considered under simply supported boundary conditions. Special attention is lead to the sensitivity of buckling load corresponding to the fibre orientation angle in comparison with the results which obtain through the Genetic Algorithm (GA) optimization frame and then Artificial Neural Network (ANN) is applied to investigate the accuracy of the optimized model. As a result, numerical CUF approach with an optimal solution demonstrates the robustness and computational efficiency of proposed optimum methodology.

Keywords: beam structures, layerwise, optimization, variable stiffness

Procedia PDF Downloads 142
2853 Constitutive Androstane Receptor (CAR) Inhibitor CINPA1 as a Tool to Understand CAR Structure and Function

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

Abstract:

This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

Procedia PDF Downloads 287