Search results for: concerns based adoption model
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 39561

Search results for: concerns based adoption model

17391 Driver Behavior Analysis and Inter-Vehicular Collision Simulation Approach

Authors: Lu Zhao, Nadir Farhi, Zoi Christoforou, Nadia Haddadou

Abstract:

The safety test of deploying intelligent connected vehicles (ICVs) on the road network is a critical challenge. Road traffic network simulation can be used to test the functionality of ICVs, which is not only time-saving and less energy-consuming but also can create scenarios with car collisions. However, the relationship between different human driver behaviors and the car-collision occurrences has been not understood clearly; meanwhile, the procedure of car-collisions generation in the traffic numerical simulators is not fully integrated. In this paper, we propose an approach to identify specific driver profiles from real driven data; then, we replicate them in numerical traffic simulations with the purpose of generating inter-vehicular collisions. We proposed three profiles: (i) 'aggressive': short time-headway, (ii) 'inattentive': long reaction time, and (iii) 'normal' with intermediate values of reaction time and time-headway. These three driver profiles are extracted from the NGSIM dataset and simulated using the intelligent driver model (IDM), with an extension of reaction time. At last, the generation of inter-vehicular collisions is performed by varying the percentages of different profiles.

Keywords: vehicular collisions, human driving behavior, traffic modeling, car-following models, microscopic traffic simulation

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17390 Membrane Bioreactor for Wastewater Treatment and Reuse

Authors: Sarra Kitanou

Abstract:

Water recycling and reuse is an effective measure to solve the water stress problem. The sustainable use of water resource has become a national development strategy in Morocco. A key aspect of improving overall sustainability is the potential for direct wastewater effluent reuse. However, the hybrid technology membrane bioreactors (MBR) have been identified as an attractive option for producing high quality and nutrient-rich effluents for wastewater treatment. It is based on complex interactions between biological processes, filtration process and rheological properties of the liquid to be treated. Currently, with the evolution of wastewater treatment projects in Morocco, the MBR technology can be used as a technology treating different types of wastewaters and to produce effluent with suitable quality for reuse. However, the energetic consumption of this process is a great concern, which can limit the development and implementation of this technology. In this investigation, the electric energy consumption of an ultrafiltration membrane bioreactor process in domestic wastewater treatment is evaluated and compared to some MBR installations based on literature review. Energy requirements of the MBR are linked to operational parameters and reactor performance. The analysis of energy consumption shows that the biological aeration and membrane filtration are more energy consuming than the other components listed as feed and recirculation pumps. Biological aeration needs 53% of the overall energetic consumption and the specific energy consumption for membrane filtration is about 25%. However, aeration is a major energy consumer, often exceeding 50% share of total energy consumption. The optimal results obtained on the MBR process (pressure p = 1.15 bar), hydraulic retention time (15 h) showed removal efficiencies up to 90% in terms of organic compounds removal, 100% in terms of suspended solids presence and up to 80% reduction of total nitrogen and total phosphorus. The effluent from this MBR system could be considered as qualified for irrigation reuse, showing its potential application in the future.

Keywords: hybrid process, membrane bioreactor, wastewater treatment, reuse

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17389 Sexual and Reproductive Rights After the Signing of the Peace Process: A Territorial Commitment

Authors: Rocio Murad, Juan Carlos Rivillas, Nury Alejandra Rodriguez, Daniela Roldán

Abstract:

In Colombia, around 5 million women have suffered forced displacement and all forms of gender-based violence, mostly adolescents and young women, single mothers, or widows with children affected by the war. After the signing of the peace agreements, the department of Antioquia has been one of the most affected by the armed conflict, from a territorial and gender perspective in the period. The objective of the research was to analyze the situation of sexual and reproductive rights in the department of Antioquia from a territorial and gender perspective in the period after the signing of the Peace Agreement. A mixed methodology was developed. The quantitative component conducted a cross-sectional descriptive study of barriers to access to contraceptive methods, safe abortion and gender-based violence based on microdata from the 2015 National Demographic and Health Survey. In the qualitative component, a case study was developed in Dabeiba, a municipality of Antioquia prioritized in order to deepen the experiences before, during and after the armed conflict in sexual and reproductive rights; using three research techniques: Focused observation, Semi-structured interviews, and Documentary review. The results showed that there is a gradient of greater vulnerability to greater effects of the conflict and that the subregion of Urabá Antioqueño, to which Dabeiba belongs, has the highest levels of vulnerability in relation to departmental data. In this subregion, the percentage of women with an unmet need for contraceptive methods (9%), women with unintended pregnancies (31%), of women between 15 and 19 years of age who are already mothers or are pregnant with their first child (32%) and the percentage of women victims of physical violence (42%) and sexual violence (13%) by their partners are significantly higher. Women, particularly rural and indigenous women, were doubly affected due to the existence of violence that is specifically directed at them or that has a greater impact on their life projects. There was evidence of insufficient, fragmented and disjointed social and institutional action in relation to women's rights and the existence of androcentric and patriarchal social imaginaries through which women and the feminine are undervalued. These results provide evidence of violations of sexual and reproductive rights in contexts of armed conflict and make it possible to identify mechanisms to guarantee the re-establishment of the rights of the victims, particularly women and girls. Among the mechanisms evidenced are: working for the elimination of gender stereotypes; supporting the formation and strengthening of women's social organizations; working for the concerted definition and articulated implementation of actions necessary to respond to sexual and reproductive health needs; and working for the recognition of reproductive violence as specific and different from sexual violence in the context of armed conflict. Also, it was evidenced that it is necessary to implement prevention, attention and reparation actions.

Keywords: sexual and reproductive rights, Colombia, armed conflict, violence against women

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17388 Teaching the Tacit Nuances of Japanese Onomatopoeia through an E-Learning System: An Evaluation Approach of Narrative Interpretation

Authors: Xiao-Yan Li, Takashi Hashimoto, Guanhong Li, Shuo Yang

Abstract:

In Japanese, onomatopoeia is an important element in the lively expression of feelings and experiences. It is very difficult for students of Japanese to acquire onomatopoeia, especially, its nuances. In this paper, based on traditional L2 learning theories, we propose a new method to improve the efficiency of teaching the nuances – both explicit and tacit - to non-native speakers of Japanese. The method for teaching the tacit nuances of onomatopoeia consists of three elements. First is to teach the formal rules representing the explicit nuances of onomatopoeic words. Second is to have the students create new onomatopoeic words by utilizing those formal rules. The last element is to provide feedback by evaluating the onomatopoeias created. Our previous study used five-grade relative estimation. However students were confused about the five-grade system, because they could not understand the evaluation criteria only based on a figure. In this new system, then, we built an evaluation database through native speakers’ narrative interpretation. We asked Japanese native speakers to describe their awareness of the nuances of onomatopoeia in writing. Then they voted on site and defined priorities for showing to learners on the system. To verify the effectiveness of the proposed method and the learning system, we conducted a preliminary experiment involving two groups of subjects. While Group A got feedback about the appropriateness of their onomatopoeic constructions from the native speakers’ narrative interpretation, Group B got feedback just in the form of the five-grade relative estimation. A questionnaire survey administered to all of the learners clarified our learning system availability and also identified areas that should be improved. Repetitive learning of word-formation rules, creating new onomatopoeias and gaining new awareness from narrative interpretation is the total process used to teach the explicit and tacit nuances of onomatopoeia.

Keywords: onomatopoeia, tacit nuance, narrative interpretation, e-learning system, second language teaching

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17387 Exploring Content of Home-Based Care Education After Caesarean Section Provided by Nurse Midwives in Maternity Units

Authors: Mdoe Mwajuma Bakari, Mselle Lilian Teddy, Kibusi Stephen Mathew

Abstract:

Background: Due to the increase of caesarean section (CS), many women are discharge early to their home. Women should be aware on how to take care of themselves at home after CS. Evidence shows non-uniform health education on home care after CS are provided to post CS mothers because of lack of standard home care guideline on home after CS; as existing guidelines explore only care of women in hospital setting, for health care workers. There is a need to develop post CS home care guide; exploring contents of home based care education after CS provided by nurse midwives will inform the development of the guide. Objective: To explore the content of health education provided by nurse midwives to post CS mother about home care after hospital discharge in Dodoma, Tanzania. Methodology: An exploratory qualitative study using in-depth interview was conducted in this study using triangulation of data collection method; where 14 nurse midwives working in maternity unit and 11 post CS mother attending their post-natal clinic were recruited. Content analysis was used to generate themes that describe health education information provided by nurse midwives to post CS mother about home care after hospital discharge. Results: The study found that, nutrition health education, maternal and newborn hygiene care of caesarean wound at home were the component of health education provided to post CS mothers by nurse midwives. Contradicting instruction were found to be provided to post CS mothers. Conclusion: This study reported non-uniform health education provided by the nurse midwives on home care after CS. Despite of the fact that nurse midwives recognizes the need to provide health education to the post CS mothers, there is a need to develop home care guideline as a reference for their education to ensure uniform package of education is provided to post CS mothers in order to improve recovery of post CS mothers from CS.

Keywords: caesarean section, home care, discharge education, homecare after caesarean section

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17386 Walmart Sales Forecasting using Machine Learning in Python

Authors: Niyati Sharma, Om Anand, Sanjeev Kumar Prasad

Abstract:

Assuming future sale value for any of the organizations is one of the major essential characteristics of tactical development. Walmart Sales Forecasting is the finest illustration to work with as a beginner; subsequently, it has the major retail data set. Walmart uses this sales estimate problem for hiring purposes also. We would like to analyzing how the internal and external effects of one of the largest companies in the US can walk out their Weekly Sales in the future. Demand forecasting is the planned prerequisite of products or services in the imminent on the basis of present and previous data and different stages of the market. Since all associations is facing the anonymous future and we do not distinguish in the future good demand. Hence, through exploring former statistics and recent market statistics, we envisage the forthcoming claim and building of individual goods, which are extra challenging in the near future. As a result of this, we are producing the required products in pursuance of the petition of the souk in advance. We will be using several machine learning models to test the exactness and then lastly, train the whole data by Using linear regression and fitting the training data into it. Accuracy is 8.88%. The extra trees regression model gives the best accuracy of 97.15%.

Keywords: random forest algorithm, linear regression algorithm, extra trees classifier, mean absolute error

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17385 An Elaborated Software Solution: The Tennis Ranking System

Authors: Dionysios Kakaroumpas, Jesseka Farago, Stephen Webber

Abstract:

Athletes and spectators depend on the tennis ranking system to represent the truest caliber of athletic prowess; a careful look at the current ranking system though, reveals its main weakness: it undermines expectations of fans and players. Our study proposes several key changes to the existing ranking formula that provide a fair and accurate approach to measure player performance. The study proposes a modification of the system to value: participation, continued advancement, and overall achievement. The new ranking formula facilitates closing the trust gap, encouraging competition equality, engaging the fan base, attracting investment, and promoting tennis involvement worldwide. To probe the crux of our main contention we performed week-by-week comparisons between results procured from the current and proposed formulae. After performing this rigorous case-study of top players of each gender, the findings strongly indicated that there is identifiable inflation in the ranks and enhanced the conviction that the current system should be updated. The new system is accompanied by a web-based software package freely available to anyone involved or interested in tennis rankings. The software package is designed to automatically calculate new player rankings based on a responsive, multi-faceted formula that also generates projected point scenarios and provides separate rankings for the three different court surfaces. By taking a critical look at the current tennis ranking system with consideration to the perspective of fans, players, and businesses involved, an upgrade is in order for it to maintain the balance of trust between fans and the evaluation process. In closure, this proposed solution increases fair play competition, eliminates rank inflation, and better engages fans, players, and sponsors by bringing in a new era of professional tennis.

Keywords: measurement and evaluation, rules and regulations, sports management and marketing, tennis ranking system

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17384 Comparing Skill, Employment, and Productivity of Industrial City Case Study: Bekasi Industrial Area and Special Economic Zone Sei Mangkei

Authors: Auliya Adzillatin Uzhma, M. Adrian Rizky, Puri Diah Santyarini

Abstract:

Bekasi Industrial Area in Kab. Bekasi and SEZ (Special Economic Zone) Sei Mangkei in Kab. Simalungun are two areas whose have the same main economic activity that are manufacturing industrial. Manufacturing industry in Bekasi Industrial Area contributes more than 70% of Kab. Bekasi’s GDP, while manufacturing industry in SEZ Sei Mangkei contributes less than 20% of Kab. Simalungun’s GDP. The dependent variable in the research is labor productivity, while the independent variable is the amount of labor, the level of labor education, the length of work and salary. This research used linear regression method to find the model for represent actual condition of productivity in two industrial area, then the equalization using dummy variable on labor education level variable. The initial hypothesis (Ho) in this research is that labor productivity in Bekasi Industrial Area will be higher than the productivity of labor in SEZ Sei Mangkei. The variable that supporting the accepted hypothesis are more labor, higher education, longer work and higher salary in Bekasi Industrial Area.

Keywords: labor, industrial city, linear regression, productivity

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17383 EFL Teachers’ Sequential Self-Led Reflection and Possible Modifications in Their Classroom Management Practices

Authors: Sima Modirkhameneh, Mohammad Mohammadpanah

Abstract:

In the process of EFL teachers’ development, self-led reflection (SLR) is thought to have an imperative role because it may help teachers analyze, evaluate, and contemplate what is happening in their classes. Such contemplations can not only enhance the quality of their instruction and provide better learning environments for learners but also improve the quality of their classroom management (CM). Accordingly, understanding the effect of teachers’ SLR practices may help us gain valuable insights into what possible modifications SLR may bring about in all aspects of EFL teachers' practitioners, especially their CM. The main purpose of this case study was, thus, to investigate the impact of SLR practices of 12 Iranian EFL teachers on their CM based on the universal classroom management checklist (UCMC). In addition, another objective of the current study was to have a clear image of EFL teachers’ perceptions of their own SLR practices and their possible outcomes. By conducting repeated reflective interviews, observations, and feedback of the participants over five teaching sessions, the researcher analyzed the outcomes qualitatively through the process of meaning categorization and data interpretation based on the principles of Grounded Theory. The results demonstrated that EFL teachers utilized SLR practices to improve different aspects of their language teaching skills and CM in different contexts. Almost all participants had positive comments and reactions about the effect of SLR on their CM procedures in different aspects (expectations and routines, behavior-specific praise, error corrections, prompts and precorrections, opportunity to respond, strengths and weaknesses of CM, teachers’ perception, CM ability, and learning process). Otherwise stated, results implied that familiarity with the UCMC criteria and reflective practices contributes to modifying teacher participants’ perceptions about their CM procedure and utilizing the reflective practices in their teaching styles. The results are thought to be valuably beneficial for teachers, teacher educators, and policymakers, who are recommended to pay special attention to the contributions as well as the complexity of reflective teaching. The study concludes with more detailed results and implications and useful directions for future research.

Keywords: classroom management, EFL teachers, reflective practices, self-led reflection

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17382 Evaluation of the Effect of Learning Disabilities and Accommodations on the Prediction of the Exam Performance: Ordinal Decision-Tree Algorithm

Authors: G. Singer, M. Golan

Abstract:

Providing students with learning disabilities (LD) with extra time to grant them equal access to the exam is a necessary but insufficient condition to compensate for their LD; there should also be a clear indication that the additional time was actually used. For example, if students with LD use more time than students without LD and yet receive lower grades, this may indicate that a different accommodation is required. If they achieve higher grades but use the same amount of time, then the effectiveness of the accommodation has not been demonstrated. The main goal of this study is to evaluate the effect of including parameters related to LD and extended exam time, along with other commonly-used characteristics (e.g., student background and ability measures such as high-school grades), on the ability of ordinal decision-tree algorithms to predict exam performance. We use naturally-occurring data collected from hundreds of undergraduate engineering students. The sub-goals are i) to examine the improvement in prediction accuracy when the indicator of exam performance includes 'actual time used' in addition to the conventional indicator (exam grade) employed in most research; ii) to explore the effectiveness of extended exam time on exam performance for different courses and for LD students with different profiles (i.e., sets of characteristics). This is achieved by using the patterns (i.e., subgroups) generated by the algorithms to identify pairs of subgroups that differ in just one characteristic (e.g., course or type of LD) but have different outcomes in terms of exam performance (grade and time used). Since grade and time used to exhibit an ordering form, we propose a method based on ordinal decision-trees, which applies a weighted information-gain ratio (WIGR) measure for selecting the classifying attributes. Unlike other known ordinal algorithms, our method does not assume monotonicity in the data. The proposed WIGR is an extension of an information-theoretic measure, in the sense that it adjusts to the case of an ordinal target and takes into account the error severity between two different target classes. Specifically, we use ordinal C4.5, random-forest, and AdaBoost algorithms, as well as an ensemble technique composed of ordinal and non-ordinal classifiers. Firstly, we find that the inclusion of LD and extended exam-time parameters improves prediction of exam performance (compared to specifications of the algorithms that do not include these variables). Secondly, when the indicator of exam performance includes 'actual time used' together with grade (as opposed to grade only), the prediction accuracy improves. Thirdly, our subgroup analyses show clear differences in the effect of extended exam time on exam performance among different courses and different student profiles. From a methodological perspective, we find that the ordinal decision-tree based algorithms outperform their conventional, non-ordinal counterparts. Further, we demonstrate that the ensemble-based approach leverages the strengths of each type of classifier (ordinal and non-ordinal) and yields better performance than each classifier individually.

Keywords: actual exam time usage, ensemble learning, learning disabilities, ordinal classification, time extension

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17381 Electroactive Fluorene-Based Polymer Films Obtained by Electropolymerization

Authors: Mariana-Dana Damaceanu

Abstract:

Electrochemical oxidation is one of the most convenient ways to obtain conjugated polymer films as polypyrrole, polyaniline, polythiophene or polycarbazole. The research in the field has been mainly directed to the study of electrical conduction properties of the materials obtained by electropolymerization, often the main reason being their use as electroconducting electrodes, and very little attention has been paid to the morphological and optical quality of the films electrodeposited on flat surfaces. Electropolymerization of the monomer solution was scarcely used in the past to manufacture polymer-based light-emitting diodes (PLED), most probably due to the difficulty of obtaining defectless polymer films with good mechanical and optical properties, or conductive polymers with well controlled molecular weights. Here we report our attempts in using electrochemical deposition as appropriate method for preparing ultrathin films of fluorene-based polymers for PLED applications. The properties of these films were evaluated in terms of structural morphology, optical properties, and electrochemical conduction. Thus, electropolymerization of 4,4'-(9-fluorenylidene)-dianiline was performed in dichloromethane solution, at a concentration of 10-2 M, using 0.1 M tetrabutylammonium tetrafluoroborate as electrolyte salt. The potential was scanned between 0 and 1.3 V on the one hand, and 0 - 2 V on the other hand, when polymer films with different structures and properties were obtained. Indium tin oxide-coated glass substrate of different size was used as working electrode, platinum wire as counter electrode and calomel electrode as reference. For each potential range 100 cycles were recorded at a scan rate of 100 mV/s. The film obtained in the potential range from 0 to 1.3 V, namely poly(FDA-NH), is visible to the naked eye, being light brown, transparent and fluorescent, and displays an amorphous morphology. Instead, the electrogrowth poly(FDA) film in the potential range of 0 - 2 V is yellowish-brown and opaque, presenting a self-assembled structure in aggregates of irregular shape and size. The polymers structure was identified by FTIR spectroscopy, which shows the presence of broad bands specific to a polymer, the band centered at approx. 3443 cm-1 being ascribed to the secondary amine. The two polymer films display two absorption maxima, at 434-436 nm assigned to π-π* transitions of polymers, and another at 832 and 880 nm assigned to polaron transitions. The fluorescence spectra indicated the presence of emission bands in the blue domain, with two peaks at 422 and 488 nm for poly (FDA-NH), and four narrow peaks at 422, 447, 460 and 484 nm for poly(FDA), peaks originating from fluorene-containing segments of varying degrees of conjugation. Poly(FDA-NH) exhibited two oxidation peaks in the anodic region and the HOMO energy value of 5.41 eV, whereas poly(FDA) showed only one oxidation peak and the HOMO level localized at 5.29 eV. The electrochemical data are discussed in close correlation with the proposed chemical structure of the electrogrowth films. Further research will be carried out to study their use and performance in light-emitting devices.

Keywords: electrogrowth polymer films, fluorene, morphology, optical properties

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17380 Genome-Wide Assessment of Putative Superoxide Dismutases in Unicellular and Filamentous Cyanobacteria

Authors: Shivam Yadav, Neelam Atri

Abstract:

Cyanobacteria are photoautotrophic prokaryotes able to grow in diverse ecological habitats, originated 2.5 - 3.5 billion years ago and brought oxygenic photosynthesis. Since then superoxide dismutases (SODs) acquired great significance due to their ability to catalyze detoxification of byproducts of oxygenic photosynthesis, i.e. superoxide radicals. Sequence information from several cyanobacterial genomes offers a unique opportunity to conduct a comprehensive comparative analysis of the superoxide dismutases family. In the present study, we extracted information regarding SODs from species of sequenced cyanobacteria and investigated their diversity, conservation, domain structure, and evolution. 144 putative SOD homologues were identified. SODs are present in all cyanobacterial species reflecting their significant role in survival. However, their distribution varies, fewer in unicellular marine strains whereas abundant in filamentous nitrogen-fixing cyanobacteria. Motifs and invariant amino acids typical in eukaryotic SODs were conserved well in these proteins. These SODs were classified into three major families according to their domain structures. Interestingly, they lack additional domains as found in proteins of other family. Phylogenetic relationships correspond well with phylogenies based on 16S rRNA and clustering occurs on the basis of structural characteristics such as domain organization. Similar conserved motifs and amino acids indicate that cyanobacterial SODs make use of a similar catalytic mechanism as eukaryotic SODs. Gene gain-and-loss is insignificant during SOD evolution as evidenced by absence of additional domain. This study has not only examined an overall background of sequence-structure-function interactions for the SOD gene family but also revealed variation among SOD distribution based on ecophysiological and morphological characters.

Keywords: comparative genomics, cyanobacteria, phylogeny, superoxide dismutases

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17379 A Study for the Effect of Fire Initiated Location on Evacuation Success Rate

Authors: Jin A Ryu, Hee Sun Kim

Abstract:

As the number of fire accidents is gradually raising, many studies have been reported on evacuation. Previous studies have mostly focused on evaluating the safety of evacuation and the risk of fire in particular buildings. However, studies on effects of various parameters on evacuation have not been nearly done. Therefore, this paper aims at observing evacuation time under the effect of fire initiated location. In this study, evacuation simulations are performed on a 5-floor building located in Seoul, South Korea using the commercial program, Fire Dynamics Simulator with Evacuation (FDS+EVAC). Only the fourth and fifth floors are modeled with an assumption that fire starts in a room located on the fourth floor. The parameter for evacuation simulations is location of fire initiation to observe the evacuation time and safety. Results show that the location of fire initiation is closer to exit, the more time is taken to evacuate. The case having the nearest location of fire initiation to exit has the lowest ratio of successful occupants to the total occupants. In addition, for safety evaluation, the evacuation time calculated from computer simulation model is compared with the tolerable evacuation time according to code in Japan. As a result, all cases are completed within the tolerable evacuation time. This study allows predicting evacuation time under various conditions of fire and can be used to evaluate evacuation appropriateness and fire safety of building.

Keywords: fire simulation, evacuation simulation, temperature, evacuation safety

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17378 Set-point Performance Evaluation of Robust ‎Back-Stepping Control Design for a Nonlinear ‎Electro-‎Hydraulic Servo System

Authors: Maria Ahmadnezhad, Seyedgharani Ghoreishi ‎

Abstract:

Electrohydraulic servo system have been used in industry in a wide ‎number of applications. Its ‎dynamics are highly nonlinear and also ‎have large extent of model uncertainties and external ‎disturbances. ‎In this thesis, a robust back-stepping control (RBSC) scheme is ‎proposed to overcome ‎the problem of disturbances and system ‎uncertainties effectively and to improve the set-point ‎performance ‎of EHS systems. In order to implement the proposed control ‎scheme, the system ‎uncertainties in EHS systems are considered as ‎total leakage coefficient and effective oil volume. In ‎addition, in ‎order to obtain the virtual controls for stabilizing system, the ‎update rule for the ‎system uncertainty term is induced by the ‎Lyapunov control function (LCF). To verify the ‎performance and ‎robustness of the proposed control system, computer simulation of ‎the ‎proposed control system using Matlab/Simulink Software is ‎executed. From the computer ‎simulation, it was found that the ‎RBSC system produces the desired set-point performance and ‎has ‎robustness to the disturbances and system uncertainties of ‎EHS systems.‎

Keywords: electro hydraulic servo system, back-stepping control, robust back-‎stepping control, Lyapunov redesign‎

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17377 Fast Prototyping of Precise, Flexible, Multiplexed, Printed Electrochemical Enzyme-Linked Immunosorbent Assay System for Point-of-Care Biomarker Quantification

Authors: Zahrasadat Hosseini, Jie Yuan

Abstract:

Point-of-care (POC) diagnostic devices based on lab-on-a-chip (LOC) technology have the potential to revolutionize medical diagnostics. However, the development of an ideal microfluidic system based on LOC technology for diagnostics purposes requires overcoming several obstacles, such as improving sensitivity, selectivity, portability, cost-effectiveness, and prototyping methods. While numerous studies have introduced technologies and systems that advance these criteria, existing systems still have limitations. Electrochemical enzyme-linked immunosorbent assay (e-ELISA) in a LOC device offers numerous advantages, including enhanced sensitivity, decreased turnaround time, minimized sample and analyte consumption, reduced cost, disposability, and suitability for miniaturization, integration, and multiplexing. In this study, we present a novel design and fabrication method for a microfluidic diagnostic platform that integrates screen-printed electrochemical carbon/silver chloride electrodes on flexible printed circuit boards with flexible, multilayer, polydimethylsiloxane (PDMS) microfluidic networks to accurately manipulate and pre-immobilize analytes for performing electrochemical enzyme-linked immunosorbent assay (e-ELISA) for multiplexed quantification of blood serum biomarkers. We further demonstrate fast, cost-effective prototyping, as well as accurate and reliable detection performance of this device for quantification of interleukin-6-spiked samples through electrochemical analytics methods. We anticipate that our invention represents a significant step towards the development of user-friendly, portable, medical-grade, POC diagnostic devices.

Keywords: lab-on-a-chip, point-of-care diagnostics, electrochemical ELISA, biomarker quantification, fast prototyping

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17376 Fast Prototyping of Precise, Flexible, Multiplexed, Printed Electrochemical Enzyme-Linked Immunosorbent Assay Platform for Point-of-Care Biomarker Quantification

Authors: Zahrasadat Hosseini, Jie Yuan

Abstract:

Point-of-care (POC) diagnostic devices based on lab-on-a-chip (LOC) technology have the potential to revolutionize medical diagnostics. However, the development of an ideal microfluidic system based on LOC technology for diagnostics purposes requires overcoming several obstacles, such as improving sensitivity, selectivity, portability, cost-effectiveness, and prototyping methods. While numerous studies have introduced technologies and systems that advance these criteria, existing systems still have limitations. Electrochemical enzyme-linked immunosorbent assay (e-ELISA) in a LOC device offers numerous advantages, including enhanced sensitivity, decreased turnaround time, minimized sample and analyte consumption, reduced cost, disposability, and suitability for miniaturization, integration, and multiplexing. In this study, we present a novel design and fabrication method for a microfluidic diagnostic platform that integrates screen-printed electrochemical carbon/silver chloride electrodes on flexible printed circuit boards with flexible, multilayer, polydimethylsiloxane (PDMS) microfluidic networks to accurately manipulate and pre-immobilize analytes for performing electrochemical enzyme-linked immunosorbent assay (e-ELISA) for multiplexed quantification of blood serum biomarkers. We further demonstrate fast, cost-effective prototyping, as well as accurate and reliable detection performance of this device for quantification of interleukin-6-spiked samples through electrochemical analytics methods. We anticipate that our invention represents a significant step towards the development of user-friendly, portable, medical-grade POC diagnostic devices.

Keywords: lab-on-a-chip, point-of-care diagnostics, electrochemical ELISA, biomarker quantification, fast prototyping

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17375 Variation in Total Iron and Zinc Concentration, Protein Quality, and Quantity of Maize Hybrids Grown under Abiotic Stress and Optimal Conditions

Authors: Tesfaye Walle Mekonnen

Abstract:

Maize is one of the most important staple food crops for most low-income households in the Sub-Saharan (SSA). Combined heat and drought stress is the major production threats that reduce the yield potential of biofortified maize and restrain various macro and micronutrient deficiencies highly prevalent in low-income people who rely solely on maize-based diets, SSA. This problem can be alleviated by crossing the biofortified inbred lines with different nutritional attributes, Fe, Zn, Protein, and Provitamin A, and developing agronomically superior and stable multi-nutrient maize of various genetic backgrounds. This aimed to understand the correlation between biofortified inbred lines per se and hybrid performance under combined heat and drought stress conditions (CSC). The experiment was conducted at CIMMYT, Zimbabwe, using α-lattice design with three replications. The hybrid effect was highly significant for zein fractions (α-, β-, γ- and δ-zein) zinc, (Zn), and iron (Fe) provitamin A, phytic acid, and grain yield. Under CSC, Fe, Zn concentration, provitamin A in grain and grain yield of hybrids were significantly decreased, however, the zein fraction content and phytic acid content increases in grain were increased under CSC. The phenotypic correlation between grain yield with Zn, Fe concentration, and Provitamin A in grain was strongly positive and higher under CSC than in well-watered conditions. The present investigation confirmed that under CSC, Fe, and Zn-enhanced hybrids could be forecasted to a certain scope based on the performance of and scientifically selected for desirable grain yield and related traits with CSC tolerance during hybrid development programs. In conclusion, the development of high-yielding and micronutrient-dense maize variety is possible under CSC, which could reduce the highly prevalent micronutrient in SSA.

Keywords: drought, Fe, heat, maize, protein, zein fractions, Zn

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17374 Competition and Cooperation of Prosumers in Cournot Games with Uncertainty

Authors: Yong-Heng Shi, Peng Hao, Bai-Chen Xie

Abstract:

Solar prosumers are playing increasingly prominent roles in the power system. However, its uncertainty affects the outcomes and functions of the power market, especially in the asymmetric information environment. Therefore, an important issue is how to take effective measures to reduce the impact of uncertainty on market equilibrium. We propose a two-level stochastic differential game model to explore the Cournot decision problem of prosumers. In particular, we study the impact of punishment and cooperation mechanisms on the efficiency of the Cournot game in which prosumers face uncertainty. The results show that under the penalty mechanism of fixed and variable rates, producers and consumers tend to take conservative actions to hedge risks, and the variable rates mechanism is more reasonable. Compared with non-cooperative situations, prosumers can improve the efficiency of the game through cooperation, which we attribute to the superposition of market power and uncertainty reduction. In addition, the market environment of asymmetric information intensifies the role of uncertainty. It reduces social welfare but increases the income of prosumers. For regulators, promoting alliances is an effective measure to realize the integration, optimization, and stable grid connection of producers and consumers.

Keywords: Cournot games, power market, uncertainty, prosumer cooperation

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17373 A Monolithic Arbitrary Lagrangian-Eulerian Finite Element Strategy for Partly Submerged Solid in Incompressible Fluid with Mortar Method for Modeling the Contact Surface

Authors: Suman Dutta, Manish Agrawal, C. S. Jog

Abstract:

Accurate computation of hydrodynamic forces on floating structures and their deformation finds application in the ocean and naval engineering and wave energy harvesting. This manuscript presents a monolithic, finite element strategy for fluid-structure interaction involving hyper-elastic solids partly submerged in an incompressible fluid. A velocity-based Arbitrary Lagrangian-Eulerian (ALE) formulation has been used for the fluid and a displacement-based Lagrangian approach has been used for the solid. The flexibility of the ALE technique permits us to treat the free surface of the fluid as a Lagrangian entity. At the interface, the continuity of displacement, velocity and traction are enforced using the mortar method. In the mortar method, the constraints are enforced in a weak sense using the Lagrange multiplier method. In the literature, the mortar method has been shown to be robust in solving various contact mechanics problems. The time-stepping strategy used in this work reduces to the generalized trapezoidal rule in the Eulerian setting. In the Lagrangian limit, in the absence of external load, the algorithm conserves the linear and angular momentum and the total energy of the system. The use of monolithic coupling with an energy-conserving time-stepping strategy gives an unconditionally stable algorithm and allows the user to take large time steps. All the governing equations and boundary conditions have been mapped to the reference configuration. The use of the exact tangent stiffness matrix ensures that the algorithm converges quadratically within each time step. The robustness and good performance of the proposed method are demonstrated by solving benchmark problems from the literature.

Keywords: ALE, floating body, fluid-structure interaction, monolithic, mortar method

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17372 Crosslinked Porous 3-Dimensional Cellulose Nanofibers/Gelatin Based Biocomposite Aerogels for Tissue Engineering Application

Authors: Ali Mirtaghavi, Andy Baldwin, Rajendarn Muthuraj, Jack Luo

Abstract:

Recent advances in biomaterials have led to utilizing biopolymers to develop 3D scaffolds in tissue regeneration. One of the major challenges of designing biomaterials for 3D scaffolds is to mimic the building blocks similar to the extracellular matrix (ECM) of the native tissues. Biopolymer based aerogels obtained by freeze-drying have shown to provide structural similarities to the ECM owing to their 3D format and a highly porous structure with interconnected pores, similar to the ECM. Gelatin (GEL) is known to be a promising biomaterial with inherent regenerative characteristics owing to its chemical similarities to the ECM in native tissue, biocompatibility abundance, cost-effectiveness and accessible functional groups, which makes it facile for chemical modifications with other biomaterials to form biocomposites. Despite such advantages, gelatin offers poor mechanical properties, sensitive enzymatic degradation and high viscosity at room temperature which limits its application and encourages its use to develop biocomposites. Hydrophilic biomass-based cellulose nanofibrous (CNF) has been explored to use as suspension for biocomposite aerogels for the development of 3D porous structures with excellent mechanical properties, biocompatibility and slow enzymatic degradation. In this work, CNF biocomposite aerogels with various ratios of CNF:GEL) (90:10, 70:30 and 50:50) were prepared by freeze-drying technique, and their properties were investigated in terms of physicochemical, mechanical and biological characteristics. Epichlorohydrin (EPH) was used to investigate the effect of chemical crosslinking on the molecular interaction of CNF: GEL, and its effects on physicochemical, mechanical and biological properties of the biocomposite aerogels. Ultimately, chemical crosslinking helped to improve the mechanical resilience of the resulting aerogels. Amongst all the CNF-GEL composites, the crosslinked CNF: GEL (70:30) biocomposite was found to be favourable for cell attachment and viability. It possessed highly porous structure (porosity of ~93%) with pore sizes ranging from 16-110 µm, adequate mechanical properties (compression modulus of ~47 kPa) and optimal biocompatibility both in-vitro and in-vivo, as well as controlled enzymatic biodegradation, high water penetration, which could be considered a suitable option for wound healing application. In-vivo experiments showed improvement on inflammation and foreign giant body cell reaction for the crosslinked CNF: GEL (70:30) compared to the other samples. This could be due to the superior interaction of CNF with gelatin through chemical crosslinking, resulting in more optimal in-vivo improvement. In-vitro cell culture investigation on human dermal fibroblasts showed satisfactory 3D cell attachment over time. Overall, it has been observed that the developed CNF: GEL aerogel can be considered as a potential scaffold for soft tissue regeneration application.

Keywords: 3D scaffolds, aerogels, Biocomposites , tissue engineering

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17371 Creating a Critical Digital Pedagogy Context: Challenges and Potential of Designing and Implementing a Blended Learning Intervention for Adult Refugees in Greece

Authors: Roula Kitsiou, Sofia Tsioli, Eleni Gana

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The current sociopolitical realities (displacement, encampment, and resettlement) refugees experience in Greece are a quite complex issue. Their educational and social ‘integration’ is characterized by transition, insecurity, and constantly changing needs. Based on the current research data, technology and more specifically mobile phones are one of the most important resources for refugees, regardless of their levels of conventional literacy. The proposed paper discusses the challenges encountered during the design and implementation of the educational Action 16 ‘Language Education for Adult Refugees’. Action 16 is one of the 24 Actions of the Project PRESS (Provision of Refugee Education and Support Scheme), funded by the Hellenic Open University (2016-2017). Project PRESS had two main objectives: a) to address the educational and integration needs of refugees in transit, who currently reside in Greece, and b) implement research-based educational interventions in online and offline sites. In the present paper, the focus is on reflection and discussion about the challenges and the potential of integrating technology in language learning for a target-group with many specific needs, which have been recorded in field notes among other research tools (ethnographic data) used in the context of PRESS. Action 16, explores if and how technology enhanced language activities in real-time and place mediated through teachers, as well as an autonomous computer-mediated learning space (moodle platform and application) builds on and expands the linguistic, cultural and digital resources and repertoires of the students by creating collaborative face-to-face and digital learning spaces. A broader view on language as a dynamic puzzle of semiotic resources and processes based on the concept of translanguaging is adopted. Specifically, designing the blended learning environment we draw on the construct of translanguaging a) as a symbolic means to valorize students’ repertoires and practices, b) as a method to reach to specific applications of a target-language that the context brings forward (Greek useful to them), and c) as a means to expand refugees’ repertoires. This has led to the creation of a learning space where students' linguistic and cultural resources can find paths to expression. In this context, communication and learning are realized by mutually investing multiple aspects of the team members' identities as educational material designers, teachers, and students on the teaching and learning processes. Therefore, creativity, humour, code-switching, translation, transference etc. are all possible means that can be employed in order to promote multilingual communication and language learning towards raising intercultural awareness in a critical digital pedagogy context. The qualitative analysis includes critical reflection on the developed educational material, team-based reflexive discussions, teachers’ reports data, and photographs from the interventions. The endeavor to involve women and men with a refugee background into a blended learning experience was quite innovative especially for the Greek context. It reflects a pragmatist ethos of the choices made in order to respond to the here-and-now needs of the refugees, and finally it was a very challenging task that has led all actors involved into Action 16 to (re)negotiations of subjectivities and products in a creative and hopeful way.

Keywords: blended learning, integration, language education, refugees

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17370 Malaysia as a Case Study for Climate Policy Integration into Energy Policy

Authors: Marcus Lee

Abstract:

The energy sector is the largest contributor of greenhouse gas emissions in Malaysia, which induces climate change. The climate change problem is therefore an energy sector problem. Tackling climate change issues successfully is contingent on actions taken in the energy sector. The researcher propounds that ‘Climate Policy Integration’ (CPI) into energy policy is a viable and insufficiently developed strategy in Malaysia that promotes the synergies between climate change and energy objectives, in order to achieve the targets found in both climate change and energy policies. In exploring this hypothesis, this paper presentation will focus on two particular aspects. Firstly, the meaning of CPI as an approach and as a concept will be explored. As an approach, CPI into energy policy means the integration of climate change objectives into the energy policy area. Its subject matter focuses on establishing the functional interrelations between climate change and energy objectives, by promoting their synergies and minimising their contradictions. However, its conceptual underpinnings are less than straightforward. Drawing from the ‘principle of integration’ found in international treaties and declarations such as the Stockholm Declaration 1972, the Rio Declaration 1992 and the United Nations Framework on Climate Change 1992 (‘UNFCCC’), this paper presentation will explore the contradictions in international standards on how the sustainable development tenets of environmental sustainability, social development and economic development are to be balanced and its relevance to CPI. Further, the researcher will consider whether authority may be derived from international treaties and declarations in order to argue for the prioritisation of environmental sustainability over the other sustainable development tenets through CPI. Secondly, this paper presentation will also explore the degree to which CPI into energy policy has been achieved and pursued in Malaysia. In particular, the strength of the conceptual framework with regard to CPI in Malaysian governance will be considered by assessing Malaysia’s National Policy on Climate Change (2009) (‘NPCC 2009’). The development (or the lack of) of CPI as an approach since the publication of the NPCC 2009 will also be assessed based on official government documents and policies that may have a climate change and/or energy agenda. Malaysia’s National Renewable Energy Policy and Action Plan (2010), draft National Energy Efficiency Action Plan (2014), Intended Nationally Determined Contributions (2015) in relation to the Paris Agreement, 11th Malaysia Plan (2015) and Biennial Update Report to the UNFCCC (2015) will be discussed. These documents will be assessed for the presence of CPI based on the language/drafting of the documents as well as the degree of subject matter regarding CPI expressed in the documents. Based on the analysis, the researcher will propose solutions on how to improve Malaysia’s climate change and energy governance. The theory of reflexive governance will be applied to CPI. The concluding remarks will be about whether CPI reflects reflexive governance by demonstrating how the governance process can be the object of shaping outcomes.

Keywords: climate policy integration, mainstreaming, policy coherence, Malaysian energy governance

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17369 Sustainability Study of Government Procurement of Public Services in Guangzhou: a Perspective Based on the Resources Dependence of Social Work

Authors: Li Pan

Abstract:

The recently prevalent government procurement of public services in China boasts a new form of government’s provision of public service through the purchasing of social work from social organizations, a new measure of the transformation in governmental functions as well as an unprecedented opportunity for the development of social organizations. For the past few years, the phenomenon of a surge in the number of social work organizations and social work staff emerged right with the initiatives of energetically carrying out the purchase of public services by the government. Such efforts have presented the strong determination of the Chinese government in building a small government by streamlining administration and delegating part of the governmental power to social organizations. This paper is based on the 2012-2014 performance appraisal project of the Guangzhou municipal government’s purchasing of public services and the project was carried out in the summer of 2015. During the process of the appraisal, several general problems hindering the sustainable development of government purchasing of public service have been observed. As Guangzhou is among the rank of pioneer cities in the conduct of the reform, it is representative and imperative to study the sustainability of government purchasing of public service. In 2012, Guangzhou local government started contracting out public service to the community social organizations to provide general family services and special services to community residents, since when integrated family service centers and special service centers were established as platforms to provide public social service in a city-wide range. Consequently, taking an example of the current rapid development of government purchase of the integrated family services and special services in Guangzhou, this paper puts up several proposals for the sustainable development of Guangzhou municipal government’s procurement of public services on the perspective of social work’s resource dependence.

Keywords: government procurement of public services, Guangzhou, integrated family service center, social work, sustainability.

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17368 Data Modeling and Calibration of In-Line Pultrusion and Laser Ablation Machine Processes

Authors: David F. Nettleton, Christian Wasiak, Jonas Dorissen, David Gillen, Alexandr Tretyak, Elodie Bugnicourt, Alejandro Rosales

Abstract:

In this work, preliminary results are given for the modeling and calibration of two inline processes, pultrusion, and laser ablation, using machine learning techniques. The end product of the processes is the core of a medical guidewire, manufactured to comply with a user specification of diameter and flexibility. An ensemble approach is followed which requires training several models. Two state of the art machine learning algorithms are benchmarked: Kernel Recursive Least Squares (KRLS) and Support Vector Regression (SVR). The final objective is to build a precise digital model of the pultrusion and laser ablation process in order to calibrate the resulting diameter and flexibility of a medical guidewire, which is the end product while taking into account the friction on the forming die. The result is an ensemble of models, whose output is within a strict required tolerance and which covers the required range of diameter and flexibility of the guidewire end product. The modeling and automatic calibration of complex in-line industrial processes is a key aspect of the Industry 4.0 movement for cyber-physical systems.

Keywords: calibration, data modeling, industrial processes, machine learning

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17367 Sustainable Urban Regenaration the New Vocabulary and the Timless Grammar of the Urban Tissue

Authors: Ruth Shapira

Abstract:

Introduction: The rapid urbanization of the last century confronts planners, regulatory bodies, developers and most of all the public with seemingly unsolved conflicts regarding values, capital, and wellbeing of the built and un-built urban space. There is an out of control change of scale of the urban form and of the rhythm of the urban life which has known no significant progress in the last 2-3 decades despite the on-growing urban population. It is the objective of this paper to analyze some of these fundamental issues through the case study of a relatively small town in the center of Israel (Kiryat-Ono, 36,000 inhabitants), unfold the deep structure of qualities versus disruptors, present some cure that we have developed to bridge over and humbly suggest a practice that may bring about a sustainable new urban environment based on timeless values of the past, an approach that can be generic for similar cases. Basic Methodologies:The object, the town of Kiryat Ono, shall be experimented upon in a series of four action processes: De-composition, Re-composition, the Centering process and, finally, Controlled Structural Disintegration. Each stage will be based on facts, analysis of previous multidisciplinary interventions on various layers – and the inevitable reaction of the OBJECT, leading to the conclusion based on innovative theoretical and practical methods that we have developed and that we believe are proper for the open ended network, setting the rules for the contemporary urban society to cluster by – thus – a new urban vocabulary based on the old structure of times passed. The Study: Kiryat Ono, was founded 70 years ago as an agricultural settlement and rapidly turned into an urban entity. In spite the massive intensification, the original DNA of the old small town was still deeply embedded, mostly in the quality of the public space and in the sense of clustered communities. In the past 20 years, the recent demand for housing has been addressed to on the national level with recent master plans and urban regeneration policies mostly encouraging individual economic initiatives. Unfortunately, due to the obsolete existing planning platform the present urban renewal is characterized by pressure of developers, a dramatic change in building scale and widespread disintegration of the existing urban and social tissue.Our office was commissioned to conceptualize two master plans for the two contradictory processes of Kiryat Ono’s future: intensification and conservation. Following a comprehensive investigation into the deep structures and qualities of the existing town, we developed a new vocabulary of conservation terms thus redefying the sense of PLACE. The main challenge was to create master plans that should offer a regulatory basis to the accelerated and sporadic development providing for the public good and preserving the characteristics of the place consisting of a tool box of design guidelines that will have the ability to reorganize space along the time axis in a sustainable way. In conclusion: The system of rules that we have developed can generate endless possible patterns making sure that at each implementation fragment an event is created, and a better place is revealed. It takes time and perseverance but it seems to be the way to provide a healthy and sustainable framework for the accelerated urbanization of our chaotic present.

Keywords: sustainable urban design, intensification, emergent urban patterns, sustainable housing, compact urban neighborhoods, sustainable regeneration, restoration, complexity, uncertainty, need for change, implications of legislation on local planning

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17366 A New Graph Theoretic Problem with Ample Practical Applications

Authors: Mehmet Hakan Karaata

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In this paper, we first coin a new graph theocratic problem with numerous applications. Second, we provide two algorithms for the problem. The first solution is using a brute-force techniques, whereas the second solution is based on an initial identification of the cycles in the given graph. We then provide a correctness proof of the algorithm. The applications of the problem include graph analysis, graph drawing and network structuring.

Keywords: algorithm, cycle, graph algorithm, graph theory, network structuring

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17365 Critical Psychosocial Risk Treatment for Engineers and Technicians

Authors: R. Berglund, T. Backström, M. Bellgran

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This study explores how management addresses psychosocial risks in seven teams of engineers and technicians in the midst of the fourth industrial revolution. The sample is from an ongoing quasi-experiment about psychosocial risk management in a manufacturing company in Sweden. Each of the seven teams belongs to one of two clusters: a positive cluster or a negative cluster. The positive cluster reports a significantly positive change in psychosocial risk levels between two time-points and the negative cluster reports a significantly negative change. The data are collected using semi-structured interviews. The results of the computer aided thematic analysis show that there are more differences than similarities when comparing the risk treatment actions taken between the two clusters. Findings show that the managers in the positive cluster use more enabling actions that foster and support formal and informal relationship building. In contrast, managers that use less enabling actions hinder the development of positive group processes and contribute negative changes in psychosocial risk levels. This exploratory study sheds some light on how management can influence significant positive and negative changes in psychosocial risk levels during a risk management process.

Keywords: group process model, risk treatment, risk management, psychosocial

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17364 Identification of Analogues to EGCG for the Inhibition of HPV E7: A Fundamental Insights through Structural Dynamics Study

Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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17363 Rationally Designed Dual PARP-HDAC Inhibitor Elicits Striking Anti-leukemic Effects

Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

Abstract:

The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

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17362 The Digitalization of Occupational Health and Safety Training: A Fourth Industrial Revolution Perspective

Authors: Deonie Botha

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Digital transformation and the digitization of occupational health and safety training have grown exponentially due to a variety of contributing factors. The literature suggests that digitalization has numerous benefits but also has associated challenges. The aim of the paper is to develop an understanding of both the perceived benefits and challenges of digitalization in an occupational health and safety context in an effort to design and develop e-learning interventions that will optimize the benefits of digitalization and address the associated challenges. The paper proposes, deliberate and tests the design principles of an e-learning intervention to ensure alignment with the requirements of a digitally transformed environment. The results of the research are based on a literature review regarding the requirements and effect of the Fourth Industrial Revolution on learning and e-learning in particular. The findings of the literature review are enhanced with empirical research in the form of a case study conducted in an organization that designs and develops e-learning content in the occupational health and safety industry. The primary findings of the research indicated that: (i) The requirements of learners and organizations in respect of e-learning are different than previously (i.e., a pre-Fourth Industrial Revolution related work setting). (ii) The design principles of an e-learning intervention need to be aligned with the entire value chain of the organization. (iii) Digital twins support and enhance the design and development of e-learning. (iv)Learning should incorporate a multitude of sensory experiences and should not only be based on visual stimulation. (v) Data that are generated as a result of e-learning interventions should be incorporated into big data streams to be analyzed and to become actionable. It is therefore concluded that there is general consensus on the requirements that e-learning interventions need to adhere to in a digitally transformed occupational health and safety work environment. The challenge remains for organizations to incorporate data generated as a result of e-learning interventions into the digital ecosystem of the organization.

Keywords: digitalization, training, fourth industrial revolution, big data

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