Search results for: al target interaction

Authors: Jose L. Diego, Antonio Berlanga, Gregorio López, Diana López

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The Rayuela method is a success story, as it is part of a project selected by the European Commission to face the challenge launched by itself for achieving a better understanding of human factors, as well as social and organisational aspects that are able to solve issues in fighting against crime. Rayuela's method specifically focuses on the drivers of cyber criminality, including approaches to prevent, investigate, and mitigate cybercriminal behavior. As the internet has become an integral part of young people’s lives, they are the key target of the Rayuela method because they (as a victim or as a perpetrator) are the most vulnerable link of the chain. Considering the increased time spent online and the control of their internet usage and the low level of awareness of cyber threats and their potential impact, it is understandable the proliferation of incidents due to human mistakes. 51% of Europeans feel not well informed about cyber threats, and 86% believe that the risk of becoming a victim of cybercrime is rapidly increasing. On the other hand, Law enforcement has noted that more and more young people are increasingly committing cybercrimes. This is an international problem that has considerable cost implications; it is estimated that crimes in cyberspace will cost the global economy $445B annually. Understanding all these phenomena drives to the necessity of a shift in focus from sanctions to deterrence and prevention. As a research project, Rayuela aims to bring together law enforcement agencies (LEAs), sociologists, psychologists, anthropologists, legal experts, computer scientists, and engineers, to develop novel methodologies that allow better understanding the factors affecting online behavior related to new ways of cyber criminality, as well as promoting the potential of these young talents for cybersecurity and technologies. Rayuela’s main goal is to better understand the drivers and human factors affecting certain relevant ways of cyber criminality, as well as empower and educate young people in the benefits, risks, and threats intrinsically linked to the use of the Internet by playing, thus preventing and mitigating cybercriminal behavior. In order to reach that goal it´s necessary an interdisciplinary consortium (formed by 17 international partners) carries out researches and actions like Profiling and case studies of cybercriminals and victims, risk assessments, studies on Internet of Things and its vulnerabilities, development of a serious gaming environment, training activities, data analysis and interpretation using Artificial intelligence, testing and piloting, etc. For facilitating the real implementation of the Rayuela method, as a community policing strategy, is crucial to count on a Police Force with a solid background in trust-building and community policing in order to do the piloting, specifically with young people. In this sense, Valencia Local Police is a pioneer Police Force working with young people in conflict solving, through providing police mediation and peer mediation services and advice. As an example, it is an official mediation institution, so agreements signed by their police mediators have once signed by the parties, the value of a judicial decision.

Keywords: fight against crime and insecurity, avert and prepare young people against aggression, ICT, serious gaming and artificial intelligence against cybercrime, conflict solving and mediation with young people

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Authors: Ildiko Fekete-Kertesz, Jade Chaker, Sylvain Berthelot, Viktoria Feigl, Monika Molnar, Lidia Favier

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There has been growing concern about emerging micropollutants in recent years, because of the possible environmental and health risk posed by these substances, which are released into the environment as a consequence of anthropogenic activities. Among them pharmaceuticals are currently not considered under water quality regulations; however, their potential effect on the environment have become more frequent in recent years. Due to the fact that these compounds can be detected in natural water matrices, it can be concluded, that the currently applied water treatment processes are not efficient enough for their effective elimination. To date, advanced oxidation processes (AOPs) are considered as highly competitive water treatment technologies for the removal of those organic micropollutants not treatable by conventional techniques due to their high chemical stability and/or low biodegradability. AOPs such as (photo)chemical oxidation and heterogeneous photocatalysis have proven their potential in degrading harmful organic compounds from aqueous matrices. However, some of these technologies generate reaction by-products, which can even be more toxic to aquatic organisms than the parent compounds. Thus, target compound removal does not necessarily result in the removal of toxicity. Therefore, to evaluate process efficiency the determination of the toxicity and ecotoxicity of the reaction intermediates is crucial to estimate the environmental risk of such techniques. In this context, the present study investigates the effectiveness of TiO2 assisted photodegradation for the removal of emerging water contaminants. Two drugs named losartan (used in high blood pressure medication) and levetiracetam (used to treat epilepsy) were considered in this work. The photocatalytic reactions were carried out with a commercial catalyst usually employed in photocatalysis. Moreover, the toxicity of the by-products generated during the process was assessed with various ecotoxicological methods applying aquatic test organisms from different trophic levels. A series of experiments were performed to evaluate the toxicity of untreated and treated solutions applying the Aliivibrio fischeri bioluminescence inhibition test, the Tetrahymena pyriformis proliferation inhibition test, the Daphnia magna lethality and immobilization tests and the Lemna minor growth inhibition test. The applied ecotoxicological methodology indicated sensitively the toxic effects of the treated and untreated water samples, hence the applied test battery is suitable for the ecotoxicological characterization of TiO2 based photocatalytic water treatment technologies and the indication of the formation of toxic by-products from the parent chemical compounds. Obtained results clearly showed that the TiO2 assisted photodegradation was more efficient in the elimination of losartan than levetiracetam. It was also observed that the treated levetiracetam solutions had more severe effect on the applied test organisms. A possible explanation would be the production of levetiracetam by-products, which are more toxic than the parent compound. The increased toxicity and the risk of formation of toxic metabolites represent one possible limitation to the implementation of photocatalytic treatment using TiO2 for the removal of losartan and levetiracetam. Our results proved that, the battery of ecotoxicity tests used in this work can be a promising investigation tool for the environmental risk assessment of photocatalytic processes.

Keywords: aquatic micropollutants, ecotoxicology, nano titanium dioxide, photocatalysis, water treatment

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Authors: Nashwa Elyamany

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In visual cultures, namely that of the United States, media representations are such influential and pervasive reflections of societal norms and expectations to the extent that they impact the manner in which both genders view themselves. Health and fitness magazines fall within the realm of visual culture. Since the main goal of communication is to ensure proper dissemination of information in order for the target audience to grasp the intended messages, it becomes imperative that magazine publishers, editors, advertisers and image producers use different modes of communication within their reach to convey messages to their readers and viewers. A rapid waxing flow of multimodality floods popular discourse, particularly health and fitness magazine cover pages. The use of well-crafted cover lines and visual images is imbued with agendas, consumerist ideologies and properties capable of effectively conveying implicit and explicit meaning to potential readers and viewers. In essence, the primary goal of this thesis is to interrogate the multi-semiotic operations and manifestations of hegemonic masculinity and femininity in male and female body culture, particularly on the cover pages of the twin American magazines Men's Health and Women's Health using corpora that spanned from 2011 to the mid of 2016. The researcher explores the semiotic resources that contribute to shaping and legitimizing a new form of postmodern, consumerist, gendered discourse that positions the reader-viewer ideologically. Methodologically, the researcher carries out analysis on the macro and micro levels. On the macro level, the researcher takes on a critical stance to illuminate the ideological nature of the multimodal ensemble of the cover pages, and, on the micro level, seeks to put forward new theoretical and methodological routes through which the semiotic choices well invested on the media texts can be more objectively scrutinized. On the macro level, a 'themes' analysis is initially conducted to isolate the overarching themes that dominate the fitness discourse on the cover pages under study. It is argued that variation in terms of frequencies of such themes is indicative, broadly speaking, of which facets of hegemonic masculinity and femininity are infused in the fitness discourse on the cover pages. On the micro level, this research work encompasses three sub-levels of analysis. The researcher follows an SF-MMDA approach, drawing on a trio of analytical frameworks: Halliday's SFG for the verbal analysis; Kress & van Leeuween's VG for the visual analysis; and CMT in relation to Sperber & Wilson's RT for the pragma-cognitive analysis of multimodal metaphors and metonymies. The data is presented in terms of detailed descriptions in conjunction with frequency tables, ANOVA with alpha=0.05 and MANOVA in the multiple phases of analysis. Insights and findings from this multi-faceted, social-semiotic analysis are interpreted in light of Cultivation Theory, Self-objectification Theory and the literature to date. Implications for future research include the implementation of a multi-dimensional approach whereby linguistic and visual analytical models are deployed with special regards to cultural variation.

Keywords: gender, hegemony, magazine cover page, multimodal discourse analysis, multimodal metaphor, multimodal metonymy, systemic functional grammar, visual grammar

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Authors: Majid Manawer Alenezi, Gavin Lawrence, Hans-Peter Kubis

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Imagery training could be an important treatment for muscle function improvements in patients who are facing limitations in exercise training by pain or other adverse symptoms. However, recent studies are mostly limited to small muscle groups and are often contradictory. Moreover, a possible bilateral transfer effect of imagery training has not been examined. We, therefore, investigated the effectiveness of unilateral imagery training in comparison with exercise training on hip abductor muscle strength and EMG. Additionally, both limbs were assessed to investigate bilateral transfer effects. Healthy individuals took part in an imagery or exercise training intervention for two weeks and were assesses pre and post training. Participants (n=30), after randomization into an imagery and an exercise group, trained 5 times a week under supervision with additional self-performed training on the weekends. The training consisted of performing, or to imagine, 5 maximal isometric hip abductor contractions (= one set), repeating the set 7 times. All measurements and trainings were performed laying on the side on a dynamometer table. The imagery script combined kinesthetic and visual imagery with internal perspective for producing imagined maximal hip abduction contractions. The exercise group performed the same number of tasks but performing the maximal hip abductor contractions. Maximal hip abduction strength and EMG amplitudes were measured of right and left limbs pre- and post-training period. Additionally, handgrip strength and right shoulder abduction (Strength and EMG) were measured. Using mixed model ANOVA (strength measures) and Wilcoxen-tests (EMGs), data revealed a significant increase in hip abductor strength production in the imagery group on the trained right limb (~6%). However, this was not reported for the exercise group. Additionally, the left hip abduction strength (not used for training) did not show a main effect in strength, however, there was a significant interaction of group and time revealing that the strength increased in the imagery group while it remained constant in the exercise group. EMG recordings supported the strength findings showing significant elevation of EMG amplitudes after imagery training on right and left side, while the exercise training group did not show any changes. Moreover, measures of handgrip strength and shoulder abduction showed no effects over time and no interactions in both groups. Experiments showed that imagery training is a suitable method for effectively increasing functional parameters of larger limb muscles (strength and EMG) which were enhanced on both sides (trained and untrained) confirming a bilateral transfer effect. Indeed, exercise training did not reveal any increases in the parameters above omitting functional improvements. The healthy individuals tested might not easily achieve benefits from exercise training within the time tested. However, it is evident that imagery training is effective in increasing the central motor command towards the muscles and that the effect seems to be segmental (no increase in handgrip strength and shoulder abduction parameters) and affects both sides (trained and untrained). In conclusion, imagery training was effective in functional improvements in limb muscles and produced a bilateral transfer on strength and EMG measures.

Keywords: imagery, exercise, physiotherapy, motor imagery

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Authors: F. Pedro, S. Dias, A. Tadeu, J. António, Ó. López, A. Coelho

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Railway transportation is considered the most economical and sustainable way to travel. However, future mobility brings important challenges to railway operators. The main target is to develop solutions that stimulate sustainable mobility. The research and innovation goals for this domain are efficient solutions, ensuring an increased level of safety and reliability, improved resource efficiency, high availability of the means (train), and satisfied passengers with the travel comfort level. These requirements are in line with the European Strategic Agenda for the 2020 rail sector, promoted by the European Rail Research Advisory Council (ERRAC). All these aspects involve redesigning current equipment and, in particular, the interior of the carriages. Recent studies have shown that two of the most important requirements for passengers are reasonable ticket prices and comfortable interiors. Passengers tend to use their travel time to rest or to work, so train interiors and their systems need to incorporate features that meet these requirements. Among the various systems that integrate train interiors, the flooring system is one of the systems with the greatest impact on passenger safety and comfort. It is also one of the systems that takes more time to install on the train, and which contributes seriously to the weight (mass) of all interior systems. Additionally, it presents a strong impact on manufacturing costs. The design of railway floor, in the development phase, is usually made relying on a design software that allows to draw and calculate several solutions in a short period of time. After obtaining the best solution, considering the goals previously defined, experimental data is always necessary and required. This experimental phase has such great significance, that its outcome can provoke the revision of the designed solution. This paper presents the methodology and some of the results of an experimental characterisation of composite panels for railway application. The mechanical tests were made for unaged specimens and for specimens that suffered some type of aging, i.e. heat, cold and humidity cycles or freezing/thawing cycles. These conditionings aim to simulate not only the time effect, but also the impact of severe environmental conditions. Both full solutions and separated components/materials were tested. For the full solution, (panel) these were: four-point bending tests, tensile shear strength, tensile strength perpendicular to the plane, determination of the spreading of water, and impact tests. For individual characterisation of the components, more specifically for the covering, the following tests were made: determination of the tensile stress-strain properties, determination of flexibility, determination of tear strength, peel test, tensile shear strength test, adhesion resistance test and dimensional stability. The main conclusions were that experimental characterisation brings a huge contribution to understand the behaviour of the materials both individually and assembled. This knowledge contributes to the increase the quality and improvements of premium solutions. This research work was framed within the POCI-01-0247-FEDER-003474 (coMMUTe) Project funded by Portugal 2020 through the COMPETE 2020.

Keywords: durability, experimental characterization, mechanical tests, railway flooring system

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Authors: Szerena Vajkovszki

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Our worldwide aging society, especially in developed countries, including members of EU, raise sophisticated sociological and economic issues and challenges to be met. As declining fertility has outstanding influence underlying this trend, numerous studies have attempted to identify, describe, measure and interpret contributing factors of the fertility rate, out of which relatively few revealed the impact of religion. Identified, examined and influential factors affecting birth rate as stated by the present scientific publications are more than a dozen out of which religious beliefs, traditions, and cultural norms were examined first with a special focus on abortion and forms of birth control. Nevertheless, connected to religion, not only these topics are crucial regarding fertility, but many others as well. Among many religious guidelines, we can separate two major categories: direct and indirect. The aim of this research was to understand what are the most crucial identified (family values, gender related behaviors, religious sentiments) and not yet identified most influential contributing religious factors. Above identifying these direct or indirect factors, it is also important to understand to what extent and how do they influence fertility, which requires a wider (inter-discipline) perspective. As proved by previous studies religion has also an influential role on health, mental state, well-being, working activity and many other components that are also related to fertility rates. All these components are inter-related. Hence direct and indirect religious effects can only be well understood if we figure out all necessary fields and their interaction. With the help of semi-structured opened interviews taking place in different countries, it was showed that indeed Buddhism has significant direct and indirect effect on fertility. Hence the initial hypothesis was proved. However, the interviews showed an overall positive effect; the results could only serve for a general understanding of how Buddhism affects fertility. Evolution of Buddhism’s direct and indirect influence may vary in different nations and circumstances according to their specific environmental attributes. According to the local patterns, with special regard to women’s position and role in the society, outstandingly indirect influences could show diversifications. So it is advisory to investigate more for a deeper and clearer understanding of how Buddhism function in different socioeconomic circumstances. For this purpose, a specific and detailed analysis was developed from recent related researches about women’s position (including family roles and economic activity) in Hungary with the intention to be able to have a complex vision of crucial socioeconomic factors influencing fertility. Further interviews and investigations are to be done in order to show a complex vision of Buddhism’s direct and indirect effect on fertility in Hungary to be able to support recommendations and policies pointing to higher fertility rates in the field of social policies. The present research could serve as a general starting point or a common basis for further specific national investigations.

Keywords: Buddhism, children, fertility, gender roles, religion, women

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Authors: Amy Williamson, Kerry Armstrong, Jason Edwards, Patricia Obst

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Australian national policy endorses a responsive approach to work health and safety (WHS) regulation, combining positive motivators (education and guidance), with compliance monitoring and enforcement to encourage and secure compliance with legislation. Despite theoretical support for responsive regulation, there is limited evidence regarding how to achieve best results in practice. Using positive psychology as a novel paradigm, this study aims to investigate how non-punitive regulatory interactions can be improved to further encourage regulatory compliance in the construction industry. As part of a larger project, semi-structured interviews were conducted with 35 inspectorate staff and 11 managers in the Australian (Queensland) construction industry. Using an inductive, grounded approach, an in-depth qualitative investigation was conducted to identify the positive psychological principles which underpin effective use of the non-punitive aspects of responsive regulation. Results highlighted the importance of effective engagement between inspectors and industry managers. This involved the need to interact cooperatively and encourage compliance with WHS legislation. Several strategies were identified that assisted regulatory interactions and the ability of inspectors to engage. The importance of communication and interpersonal skills was reported to be critical to any interaction, regardless of the nature of the visit and regulatory tools used. In particular, the use of clear and open communication fostered trust and rapport which facilitated more positive interactions. The importance of respect and empathy was also highlighted. The need for provision of guidance and direction on how to achieve compliance was also reported. This related to ensuring companies understand their WHS obligations, providing specific advice regarding how to rectify a breach and meet compliance requirements, and ensuring sufficient follow up to confirm that compliance is successfully achieved. In the absence of imminent risk, allowing companies the opportunity to comply before further action is taken was also highlighted. Increased proactive engagement with industry to educate and promote the vision of safety at work was also reported. Finally, provision of praise and positive feedback was reported to assist interactions and encourage the continuation of good practices. Evidence from positive psychology and organisational psychology was obtained to support the use of each strategy in practice. In particular, the area of positive leadership provided a useful framework to consider the factors and conditions that drive positive interactions within the context of work health and safety and the specific relationship between inspectors and industry managers. This study provides fresh insight into key psychological principles which support non-punitive regulatory interactions in the area of workplace health and safety. The findings of this research contribute to a better understanding of how inspectors can enhance the efficacy of their regulatory interactions to improve compliance with legislation. Encouraging and assisting compliance through effective non-punitive activity offers a sustainable pathway for promoting safety and preventing fatalities and injuries in the construction industry.

Keywords: engagement, non-punitive approaches to compliance, positive interactions in the workplace, work health and safety compliance

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Authors: Nadeesha Sewwandi, Dilini Shashikala, R. Kanapathy, S. Viyasan, R. M. S. Kumara, Duminda Guruge

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Early childhood development is important to the emotional, social, and physical development of young children and it has a direct effect on their overall development and on the adult they become. Play is so important to optimal child developments including skill development, social development, imagination, creativity and it fulfills a baby’s inborn need to learn. So, health promotion approach empowers people about the development of early childhood. Play area is a new concept and this study focus how this play areas helps to the development of early childhood of children in rural villages in Sri Lanka. This study was conducted with a children society in a rural village called Welankulama in Sri Lanka. Survey was conducted with children society about emotional, social and physical development of young children (Under age eight) in this village using questionnaires. It described most children under eight years age have poor level of emotional, social and physical development in this village. Then children society wanted to find determinants for this problem and among them they prioritized determinants like parental interactions, learning environment and social interaction and address them using an innovative concept called play area. In this village there is a common place as play area under a big tamarind tree. It consists of a playhouse, innovative playing toys, mobile library, etc. Twice a week children, parents, grandparents gather to this nice place. Collective feeding takes place in this area once a week and it was conducted by several mothers groups in this village. Mostly grandparents taught about handicrafts and this is a very nice place to share their experiences with all. Healthy competitions were conducted in this place through playing to motivate the children. Happy calendar (mood of the children) was marked by children before and after coming to the play area. In terms of results qualitative changes got significant place in this study. By learning about colors and counting through playing the thinking and reasoning skills got developed among children. Children were widening their imagination by means of storytelling. We observed there were good developments of fine and gross motor skills of two differently abled children in this village. Children learn to empathize with other people, sharing, collaboration, team work and following of rules. And also children gain knowledge about fairness, through role playing, obtained insight on the right ways of displaying emotions such as stress, fear, anger, frustration, and develops knowledge of how they can manage their feelings. The reading and writing ability of the children got improved by 83% because of the mobile library. The weight of children got increased by 81% in the village. Happiness was increased by 76% among children in the society. Playing is very important for learning during early childhood period of a person. Health promotion interventions play a major role to the development of early childhood and it help children to adjust to the school setting and even to enhance children’s learning readiness, learning behaviors and problem solving skills.

Keywords: early childhood development, health promotion approach, play and learning, working with children

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Authors: Jens Hagman, Jenny Janhager Stier, Ellen Olausson, Anne Y. Faxer, Ana Magazinius

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Sweden has the second highest electric vehicle (plug-in hybrid and battery electric vehicle) sales per capita in Europe but in relation to sales of internal combustion engine electric vehicles sales are still minuscular (< 4%). Much research effort has been placed on various technical and user focused barriers and enablers for adoption of electric vehicles. Less effort has been placed on investigating the retail (dealership-customer) sales process of vehicles in general and electric vehicles in particular. Arguably, no one ought to be better informed about needs and desires of potential electric vehicle buyers than car salesmen, originating from their daily encounters with customers at the dealership. The aim of this paper is to explore the conditions of selling electric vehicle from a car salesmen’s perspective. This includes identifying barriers and enablers for electric vehicle sales originating from internal (dealership and brand) and external (customer, government) sources. In this interview study five car brands (manufacturers) that sell both electric and internal combustion engine vehicles have been investigated. A total of 15 semi-structured interviews have been conducted (three per brand, in rural and urban settings and at different dealerships). Initial analysis reveals several barriers and enablers, experienced by car salesmen, which influence electric vehicle sales. Examples of as reported by car salesmen identified barriers are: -Electric vehicles earn car salesmen less commission on average compared to internal combustion engine vehicles. -It takes more time to sell and deliver an electric vehicle than an internal combustion engine vehicle. -Current leasing contracts entails relatively low second-hand value estimations for electric vehicles and thus a high leasing fee, which negatively affects the attractiveness of electric vehicles for private consumers in particular. -High purchasing price discourages many consumers from considering electric vehicles. -The education and knowledge level of electric vehicles differs between car salesmen, which could affect their self-confidence in meeting well prepared and question prone electric vehicle buyers. Examples of identified enablers are: -Company car tax regulation promotes sales of electric vehicles; in particular, plug-in hybrid electric vehicles are sold extensively to companies (up to 95 % of sales). -Low operating cost of electric vehicles such as fuel and service is an advantage when understood by consumers. -The drive performance of electric vehicles (quick, silent and fun to drive) is attractive to consumers. -Environmental aspects are considered important for certain consumer groups. -Fast technological improvements, such as increased range are opening up a wider market for electric vehicles. -For one of the brands; attractive private lease campaigns have proved effective to promote sales. This paper gives insights of an important but often overlooked aspect for the diffusion of electric vehicles (and durable products in general); the interaction between car salesmen and customers at the critical acquiring moment. Extracted through interviews with multiple car salesmen. The results illuminate untapped potential for sellers (salesmen, dealerships and brands) to mitigating sales barriers and strengthening sales enablers and thus becoming a more important actor in the electric vehicle diffusion process.

Keywords: customer barriers, electric vehicle promotion, sales of electric vehicles, interviews with car salesmen

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Authors: Jianli Jiang, Bai-Chen Xie

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The climate issue has aroused global concern. Achieving sustainable development is a good path for countries to mitigate environmental and climatic pressures, although there are many difficulties. The first step towards sustainable development is to evaluate the environmental efficiency of the energy industry with proper methods. The power sector is a major source of CO2, SO2, and NOx emissions. Evaluating the environmental efficiency (EE) of power systems is the premise to alleviate the terrible situation of energy and the environment. Data Envelopment Analysis (DEA) has been widely used in efficiency studies. However, measuring the efficiency of a system (be it a nation, region, sector, or business) is a challenging task. The classic DEA takes the decision-making units (DMUs) as independent, which neglects the interaction between DMUs. While ignoring these inter-regional links may result in a systematic bias in the efficiency analysis; for instance, the renewable power generated in a certain region may benefit the adjacent regions while the SO2 and CO2 emissions act oppositely. This study proposes a spatial network DEA (SNDEA) with a slack measure that can capture the spatial spillover effects of inputs/outputs among DMUs to measure efficiency. This approach is used to study the EE of China's power system, which consists of generation, transmission, and distribution departments, using a panel dataset from 2014 to 2020. In the empirical example, the energy and patent inputs, the undesirable CO2 output, and the renewable energy (RE) power variables are tested for a significant spatial spillover effect. Compared with the classic network DEA, the SNDEA result shows an obvious difference tested by the global Moran' I index. From a dynamic perspective, the EE of the power system experiences a visible surge from 2015, then a sharp downtrend from 2019, which keeps the same trend with the power transmission department. This phenomenon benefits from the market-oriented reform in the Chinese power grid enacted in 2015. The rapid decline in the environmental efficiency of the transmission department in 2020 was mainly due to the Covid-19 epidemic, which hinders economic development seriously. While the EE of the power generation department witnesses a declining trend overall, this is reasonable, taking the RE power into consideration. The installed capacity of RE power in 2020 is 4.40 times that in 2014, while the power generation is 3.97 times; in other words, the power generation per installed capacity shrank. In addition, the consumption cost of renewable power increases rapidly with the increase of RE power generation. These two aspects make the EE of the power generation department show a declining trend. Incorporation of the interactions among inputs/outputs into the DEA model, this paper proposes an efficiency evaluation method on the basis of the DEA framework, which sheds some light on efficiency evaluation in regional studies. Furthermore, the SNDEA model and the spatial DEA concept can be extended to other fields, such as industry, country, and so on.

Keywords: spatial network DEA, environmental efficiency, sustainable development, power system

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Authors: David Tennison

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Epistemic injustice, an injustice done to a person specifically in their capacity as a “knower”, is a subtle form of discrimination, yet its effects can be as dehumanizing and damaging as more overt forms of discrimination. The lens of epistemic injustice has, in recent years, been fruitfully applied to the field of healthcare, examining questions of agency, power, credibility and belief in doctor-patient interactions. Contested illness patients (e.g., those with illnesses lacking scientific consensuses such as fibromyalgia (FM), Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) and Long Covid) face higher levels of scrutiny than other patient groups and are often disbelieved or dismissed when their ailments cannot be easily imaged or tested for- often encapsulated by the expression “it’s all in your head”. Using the case study of FM, the trials of contested illness patients in healthcare can be conceptualized in terms of epistemic injustice, and what is going wrong in these doctor-patient relationships can be effectively diagnosed. This case study also helps reveal epistemic dysfunction (structural epistemic issues embedded in the healthcare system), how this relates to stigma identity-based prejudice, and how the healthcare system upholds existing societal hierarchies and disenfranchises the most vulnerable. In the modern landscape, where cases of these chronic illnesses are not only on the rise but future pandemics threaten to add to their number, this conversation is crucial for the well-being of patients and providers. This presentation will cover what epistemic injustice is and how it can be applied to the politics of the doctor-patient interaction on a micro level and the politics of the healthcare system more broadly. Contested illnesses will be explored in terms of how the “contested” label causes the patient to experience disease stigma and lowers their credibility in healthcare and across other aspects of life. This will be explored in tandem with a discussion of existing identity-based prejudice in the healthcare system and how social identities (such as those of gender, race, and socioeconomic status) intersect with the contested illness label. The effects of epistemic injustice, which include worsening patients’ symptoms of mental health and potentially disenfranchising them from the healthcare system altogether, will be presented alongside the potential ethical quandaries this poses for providers. Finally, issues with the way healthcare appointments and the modern NHS function will be explored in terms of epistemic injustice and solutions to improve doctor-patient communication and patient care will be discussed. The relationship between contested illness patients and healthcare providers is notoriously poor, and while this can mean frustration or feelings of unfulfillment in providers, the negative effects for patients are much more severe. The purpose of this research, then, is to highlight these issues and suggest ways in which to improve the healthcare experience for these patients, along with improving doctor-patient communication and mending the doctor-patient relationship in a tangible and realistic way. This research also aims to provoke important conversations about belief and hierarchy in medical settings and how these aspects intersect with identity prejudices.

Keywords: epistemic injustice, fibromyalgia, contested illnesses, chronic illnesses, doctor-patient relationships, philosophy of medicine

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Authors: Collen Tebogo Masilo, Erik Schmikl

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The demand for the DataMiner product by customers has presented a great challenge for the vendor in Skyline Communications in deploying its limited resources in the form of human resources, financial resources, and office space, to achieve high organisational performance in all its international operations. The rapid growth of the organisation has been unable to efficiently support its existing customers across the globe, and provide services to new customers, due to the limited number of approximately one hundred employees in its employ. The combined descriptive and explanatory case study research methods were selected as research design, making use of a survey questionnaire which was distributed to a sample of 100 respondents. A sample return of 89 respondents was achieved. The sampling method employed was non-probability sampling, using the convenient sampling method. Frequency analysis and correlation between the subscales (the four themes) were used for statistical analysis to interpret the data. The investigation was conducted into mechanisms that can be deployed to balance the high demand for products and the limited production capacity of the company’s Belgian operations across four aspects: demand management strategies, capacity management strategies, communication methods that can be used to align a sales management department, and reward systems in use to improve employee performance. The conclusions derived from the theme ‘demand management strategies’ are that the company is fully aware of the future market demand for its products. However, there seems to be no evidence that there is proper demand forecasting conducted within the organisation. The conclusions derived from the theme 'capacity management strategies' are that employees always have a lot of work to complete during office hours, and, also, employees seem to need help from colleagues with urgent tasks. This indicates that employees often work on unplanned tasks and multiple projects. Conclusions derived from the theme 'communication methods used to align sales management department with operations' are that communication is not good throughout the organisation. This means that information often stays with management, and does not reach non-management employees. This also means that there is a lack of smooth synergy as expected and a lack of good communication between the sales department and the projects office. This has a direct impact on the delivery of projects to customers by the operations department. The conclusions derived from the theme ‘employee reward systems’ are that employees are motivated, and feel that they add value in their current functions. There are currently no measures in place to identify unhappy employees, and there are also no proper reward systems in place which are linked to a performance management system. The research has made a contribution to the body of research by exploring the impact of the four sub-variables and their interaction on the challenges of organisational productivity, in particular where an organisation experiences a capacity problem during its growth stage during tough economic conditions. Recommendations were made which, if implemented by management, could further enhance the organisation’s sustained competitive operations.

Keywords: high demand for products, high organisational performance, limited production capacity, limited resources

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Authors: Livia Calcagni

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Most of the largest cities in the world are located in areas that are vulnerable to coastal erosion and flooding, both linked to climate change and rising sea levels (RSL). Nevertheless, more and more people are moving to these vulnerable areas as cities keep growing. Architects, engineers and policy makers are called to rethink the way we live and to provide timely and adequate responses not only by investigating measures to improve the urban fabric, but also by developing strategies capable of planning change, exploring unusual and resilient frontiers of living, such as floating architecture. Since the beginning of the 21st century we have seen a dynamic growth of water-based architecture. At the same time, the shortage of land available for urban development also led to reclaim the seabed or to build floating structures. In light of these considerations, time is ripe to consider floating architecture not only as a full-fledged building typology but especially as a full-fledged adaptation solution for RSL. Currently, there is no global international legal framework for urban development on water and there is no structured performance based building design (PBBD) approach for floating architecture in most countries, let alone national regulatory systems. Thus, the research intends to identify the technological, morphological, functional, economic, managerial requirements that must be considered in a the development of the PBBD framework conceived as a meta-design tool. As it is expected that floating urban development is mostly likely to take place as extension of coastal areas, the needs and design criteria are definitely more similar to those of the urban environment than of the offshore industry. Therefor, the identification and categorization of parameters takes the urban-architectural guidelines and regulations as the starting point, taking the missing aspects, such as hydrodynamics, from the offshore and shipping regulatory frameworks. This study is carried out through an evidence-based assessment of performance guidelines and regulatory systems that are effective in different countries around the world addressing on-land and on-water architecture as well as offshore and shipping industries. It involves evidence-based research and logical argumentation methods. Overall, this paper highlights how inhabiting water is not only a viable response to the problem of RSL, thus a resilient frontier for urban development, but also a response to energy insecurity, clean water and food shortages, environmental concerns and urbanization, in line with Blue Economy principles and the Agenda 2030. Moreover, the discipline of architecture is presented as a fertile field for investigating solutions to cope with climate change and its effects on life safety and quality. Future research involves the development of a decision support system as an information tool to guide the user through the decision-making process, emphasizing the logical interaction between the different potential choices, based on the PBBD.

Keywords: adaptation measures, floating architecture, performance based building design, resilient architecture, rising sea levels

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Authors: Arif Ahmed Mohammed Al-Ahdal

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Poetry, tales, and fables have always been a part of the L1 repertoire and one that takes the learners to another amazing and fascinating world of imagination. The storytelling class and the genre of poems are activities greatly enjoyed by all age groups. The very significant idea behind their inclusion in the language curriculum is to sensitize young minds to a wide range of human emotions that are believed to greatly contribute to building their social resilience, emotional stability, empathy towards fellow creatures, and literacy. Quite certainly, the learning objective at this stage is not language acquisition (though it happens as an automatic process) but getting the young learners to be acquainted with an entire spectrum of what may be called the ‘noble’ abilities of the human race. They enrich their very existence, inspiring them to unearth ‘selves’ that help them as adults and enable them to co-exist fruitfully and symbiotically with their fellow human beings. By extension, ‘higher’ training in these literature genres shows the universality of human emotions, sufferings, aspirations, and hopes. The current study is anchored on the Reader-Response-Theory in literature learning, which suggests that the reader reconstructs work and re-enacts the author's creative role. Reiteratingly, literary works provide clues or verbal symbols in a linguistic system, widely accepted by everyone who shares the language, but everyone reads their own life experiences and situations into them. The significance of words depends on the reader, even if they have a typical relationship. In every reading, there is an interaction between the reader and the text. The process of reading is an experience in which the reader tries to comprehend the literary work, which surpasses its full potential since it provides emotional and intellectual reactions that are not anticipated from the document but cannot be affirmed just by the reader as a part of the text. The idea is that the text forms the basis of a unifying experience. A reinterpretation of the literary text may transform it into a guiding principle to respond to actual experiences and personal memories. The impulses delivered to the reader vary according to poetry or texts; nevertheless, the readers differ considerably even with the same material. Previous studies confirm that poetry is a useful tool for learning a language. This present paper works on these hypotheses and proposes to study the impetus given to L2 learning as a factor of exposure to poetry and meaningful stories in L1. The driving force behind the choice of this topic is the first-hand experience that the researcher had while teaching a literary text to a group of BA students who, as a reaction to the text, initially burst into tears and ultimately turned the class into an interactive session. The study also intends to compare the performance of male and female students post intervention using pre and post-tests, apart from undertaking a detailed inquiry via interviews with college learners of English to understand how L1 literature plays a great role in the acquisition of L2.

Keywords: SLA, literary text, poetry, tales, affective factors

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

Procedia PDF Downloads 279

Authors: Mirele Plenishti

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Revisionist powers are sometimes associated to revolutionary and status quo powers, this because along the line representing the level of satisfaction–dissatisfaction with the system, revisionist powers are located in between status quo and revolutionary powers. In particular, the case of revisionist powers seeking for social status adjustments (while having status quo intentions) can, in the first option, be refuted due to the disbelief that dissatisfaction could coexist with status quo intentions – this entailing the possibility to trigger a spiral effect by over-counter-reacting. In the second option, revisionist powers can be underestimated as a real threat, this entailing a potential inadequate reaction. The necessity to well manage international change entails the need to understand better how revisionist powers seek for changes in status, within the system. The complexity of this case is heightened by the propensity of both IR scholars and practitioners to infer states' aims and intentions – towards the system – by looking at their behaviours. This has resulted in the tendency to consider cooperative international behaviours as symptomatic of status quo intentions, and vice versa: status quo intentions as manifested through positive/cooperative behaviours. Similarly, assertive/competitive international behaviours are considered as symptomatic (and vice versa, as manifestations) of revolutionary intentions. Therefore, within complex and composite foreign policies, scholars who disbelieve the existence of revisionist powers with status quo intentions, tend to highlight the negative/competitive elements; while more optimist scholars tend to focus on conforming/cooperative behaviours. Both perspectives, while understanding relevant components of the complex international interaction, still miss a composite overview. In order to closely investigate the strategies adopted by (status quo aiming) revisionist states, and by drawing on sociological studies on peer relations, focused on children's behaviour, one could expect that the compresence of both positive (compliant/cooperative) and negative (competitive/assertive) behaviours, is deliberate, and functional to seeking social status adjustments. Indeed, at the end of 90s, peer relation studies focused on children's behaviour, discerned between the concept of social acceptance (that refers to the degree of social preference assigned to the child– how much is s/he liked) and popularity (which refers to the social status assigned to the child within the group). By building on this distinction, it was possible to identify a link relating social acceptance to prosocial (compliant/cooperative) behaviours and strategies, and popularity to both prosocial and antisocial (aggressive/assertive) behaviours and strategies. Since then, antisocial behaviours ceased to be considered as a proof of social maladjustment and were finally identified as socially recognized strategies adopted in function of the achievement of popularity. Drawing on these results, one can hypothesize that also international status seekers perform both positive (conforming/compliant/cooperative) and negative (assertive/aggressive/competitive) behaviours. Therefore, the link between aims and behaviours loses its strength, since cooperative and competitive behaviours are both means for status seeking strategies that aim at status quo intentions. By carrying out a historical investigation of Italy's foreign policy during fascism, the intent is to closely look at this compresence of behaviours, in order to better qualify its components and their relations.

Keywords: compresence of cooperative and competitive behaviours and strategies, revisionist powers, status quo intentions, status seeking

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Authors: Martina Maria Keitsch, Sangeeta Singh

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There has been a growing recognition that sustainable development needs to consider economic, social and environmental aspects including gender. In Nepal, the majority of the population lives in rural areas, and many households do not have access to electricity. In rural areas, the difficulty of accessing energy is becoming one of the greatest constraints for improving living conditions. This is particularly true for women and children, who spent much time for collecting firewood and cooking and thus are often deprived of time for education, political- and business activities. The poster introduces an education and research project financed by the Norwegian Government. The project runs from 2015-2020 and is a collaboration between the Norwegian University of Science (NTNU) and Technology Institute of Engineering (IOE), Tribhuvan University. It has the title Master program and Research in Energy for Sustainable Social Development Energy for Sustainable Social Development (MSESSD). The project addresses engineering and architecture students and comprises several integral activities towards gender mainstreaming. The following activities are conducted; 1. Creating academic opportunities, 2. Updating administrative personnel on strategies to effectively include gender issues, 3. Integrating female and male stakeholders in the design process, 4. Sensitizing female and male students for gender issues in energy systems. The project aims to enable students to design end-user-friendly solutions which can, for example, save time that can be used to generate and enhance income. Relating to gender mainstreaming, design concepts focus on smaller-scale technologies, which female stakeholders can take control of and manage themselves. Creating academic opportunities, we have a 30% female students’ rate in each master student batch in the program with the goal to educate qualified female personnel for academia and policy-making/government. This is a very ambitious target in a Nepalese context. The rate of female students, who completed the MSc program at IOE between 1998 and January 2015 is 10% out of 180 students in total. For recruiting, female students were contacted personally and encouraged to apply for the program. Further, we have established a Master course in gender mainstreaming and energy. On an administrative level, NTNU has hosted a training program for IOE on gender-mainstreaming information and -strategies for academic education. Integrating female and male stakeholders, local women groups such as, e.g., mothers group are actively included in research and education for example in planning, decision-making, and management to establish clean energy solutions. The project meets women’s needs not just practically by providing better technology, but also strategically by providing solutions that enhance their social and economic decision-making authority. Sensitizing the students for gender issues in energy systems, the project makes it mandatory to discuss gender mainstreaming based on the case studies in the Master thesis. All activities will be discussed in detail comprising an overview of MSESSD, the gender mainstreaming master course contents’, and case studies where energy solutions were co-designed with men and women as lead-users and/or entrepreneurs. The goal is to motivate educators to develop similar forms of transnational gender collaboration.

Keywords: knowledge generation on gender mainstreaming, sensitizing students, stakeholder inclusion, education strategies for design and architecture in gender mainstreaming, facilitation for cooperation

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Authors: Susan C. Graham

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Authenticity has grown to be ubiquitous within the tourism vernacular. Yet, agreement regarding what authenticity means in relation to tourism remains nebulous. In its simplest form, authenticity in tourism refers to products and experiences that provide insights into the social, cultural, economic, natural, historical, and political life of a place. But this definition is unwieldy in its scope and may not help industry leaders nor tourist in identifying that which is authentic. Much of what is projected as authentic is a carefully curated and crafted message developed by marketers to appeal to visitors and bears little resemblance to the everyday lives of locals. So perhaps one way to identify authentic tourism experiences is to ask locals themselves. The purpose of this study was to explore the perspectives of locals with respect to what constituted an authentic tourism experience in Prince Edward Island (PEI), Canada. Over 600 volunteers in a tourism research panel were sent a survey asking them to describe authentic PEI experiences within ten sub-categories relevant to the local tourism industry. To make participation more manageable, each respondent was asked their perspectives on any three of the tourism sub-categories. Over 400 individuals responded, providing 1391 unique responses. The responses were grouped thematically using interpretive phenomenological analysis whereby the participants’ responses were clustered into higher order groups to extract meaning. Two interesting thematic observations emerged: first, that respondents tended to clearly articulate and differentiate between intra- versus interpersonal experiences as a means of authentically experiencing PEI; and second, while respondents explicitly valued unstaged experiences over staged, several exceptions to this general rule were expressed. Responses could clearly be grouped into those that emphasized “going off the beaten path,” “exploring pristine and untouched corners,” “lesser known,” “hidden”, “going solo,” and taking the opportunity to “slow down.” Each of these responses was “self” centered, and focused on the visitor discovering and exploring in search of greater self-awareness and inner peace. In contrast, other responses encouraged the interaction of visitors with locals as a means of experiencing the authentic place. Respondents sited “going deep-sea fishing” to learn about local fishers and their communities, stopping by “local farm stands” and speaking with farmers who worked the land for generations,” patronizing “local restaurants, pubs, and b&bs”, and partaking in performances or exhibits by local artists. These kinds of experiences, the respondents claimed, provide an authentic glimpse into a place’s character. The second set of observations focused on the distinction between staged and unstaged experiences, with respondents overwhelmingly advocating for unstaged. Responses were clear in shunning “touristy,” “packaged,” and “fake” offerings for being inauthentic and misrepresenting the place as locals view it. Yet many respondents made exceptions for certain “staged” experiences, including (quite literally) the stage production of Anne of Green Gables based on the novel of the same name, the theatrical re-enactment of the founding of Canada, and visits to PEI’s many provincial and national parks, all of which respondents considered both staged and authentic at the same time.

Keywords: authentic, local, Prince Edward Island, tourism

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Authors: Monika Saha, A. T. M. Hasan Zobeyer, Nasreen Jahan

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El Nino-Southern Oscillation (ENSO) is the interaction between atmosphere and ocean in tropical Pacific which causes inconsistent warm/cold weather in tropical central and eastern Pacific Ocean. Due to the impact of climate change, ENSO events are becoming stronger in recent times, and therefore it is very important to study the influence of ENSO in climate studies. Bangladesh, being in the low-lying deltaic floodplain, experiences the worst consequences due to flooding every year. To reduce the catastrophe of severe flooding events, non-structural measures such as flood forecasting can be helpful in taking adequate precautions and steps. Forecasting seasonal flood with a longer lead time of several months is a key component of flood damage control and water management. The objective of this research is to identify the possible strength of teleconnection between ENSO and river flow of Surma and examine the potential possibility of long lead flood forecasting in the wet season. Surma is one of the major rivers of Bangladesh and is a part of the Surma-Meghna river system. In this research, sea surface temperature (SST) has been considered as the ENSO index and the lead time is at least a few months which is greater than the basin response time. The teleconnection has been assessed by the correlation analysis between July-August-September (JAS) flow of Surma and SST of Nino 4 region of the corresponding months. Cumulative frequency distribution of standardized JAS flow of Surma has also been determined as part of assessing the possible teleconnection. Discharge data of Surma river from 1975 to 2015 is used in this analysis, and remarkable increased value of correlation coefficient between flow and ENSO has been observed from 1985. From the cumulative frequency distribution of the standardized JAS flow, it has been marked that in any year the JAS flow has approximately 50% probability of exceeding the long-term average JAS flow. During El Nino year (warm episode of ENSO) this probability of exceedance drops to 23% and while in La Nina year (cold episode of ENSO) it increases to 78%. Discriminant analysis which is known as 'Categoric Prediction' has been performed to identify the possibilities of long lead flood forecasting. It has helped to categorize the flow data (high, average and low) based on the classification of predicted SST (warm, normal and cold). From the discriminant analysis, it has been found that for Surma river, the probability of a high flood in the cold period is 75% and the probability of a low flood in the warm period is 33%. A synoptic parameter, forecasting index (FI) has also been calculated here to judge the forecast skill and to compare different forecasts. This study will help the concerned authorities and the stakeholders to take long-term water resources decisions and formulate policies on river basin management which will reduce possible damage of life, agriculture, and property.

Keywords: El Nino-Southern Oscillation, sea surface temperature, surma river, teleconnection, cumulative frequency distribution, discriminant analysis, forecasting index

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Authors: Andrés Quiroz, Emilio Hormazabal, Ana Mutis, Fernando Ortega, Manuel Chacón-Fuentes, Leonardo Parra

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Red clover (Trifolium pratense L.) is an important forage species in temperate regions of the world. The main limitation of this species worldwide is a lack of persistence related to the high mortality of plants due to a complex of biotic and abiotic factors, determining a life span of two or three seasons. Because of the importance of red clover in Chile, a red clover breeding program was started at INIA Carillanca Research Center in 1989, with the main objective of improving the survival of plants, forage yield, and persistence. The main selection criteria for selecting new varieties have been based on agronomical parameters and biotic factors. The main biotic factor associated with red clover mortality in Chile is Hylastinus obscurus (Coleoptera: Curculionidae). Both larval and adults feed on the roots, causing weakening and subsequent death of clover plants. Pesticides have not been successful for controlling infestations of this root borer. Therefore, alternative strategies for controlling this pest are a high priority for red clover producers. Currently, the role of semiochemical in the interaction between H. obscurus and red clover plants has been widely studied for our group. Specifically, from the red clover foliage has been identified limonene is eliciting repellency from the root borer. Limonene is generated in the plant from two independent biosynthetic pathways, the mevalonic acid, and deoxyxylulose pathway. Mevalonate pathway enzymes are localized in the cytosol, whereas the deoxyxylulose phosphate pathway enzymes are found in plastids. In summary, limonene can be determinated by enzymatic bioassay using GPP as substrate and by limonene synthase expression. Therefore, the main objective of this work was to study genetic variation of limonene in material provided by INIA´s Red Clover breeding program. Protein extraction was carried out homogenizing 250 mg of leave tissue and suspended in 6 mL of extraction buffer (PEG 1500, PVP-30, 20 mM MgCl2 and antioxidants) and stirred on ice for 20 min. After centrifugation, aliquots of 2.5 mL were desalted on PD-10 columns, resulting in a final volume of 3.5 mL. Protein determination was performed according to Bradford with BSA as a standard. Monoterpene synthase assays were performed with 50 µL of protein extracts transferred into gas-tight 2 mL crimp seal vials after addition of 4 µL MgCl₂ and 41 µL assay buffer. The assay was started by adding 5 µL of a GPP solution. The mixture was incubated for 30 min at 40 °C. Biosynthesized limonene was quantified in a GC equipped with a chiral column and using synthetic R and S-limonene standards. The enzymatic the production of R and S-limonene from different Superqueli-Carillanca genotypes is shown in this work. Preliminary results showed significant differences in limonene content among the genotypes analyzed. These results constitute an important base for selecting genotypes with a high content of this repellent monoterpene towards H. obscurus.

Keywords: head space, limonene enzymatic determination, red clover, Hylastinus obscurus

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Authors: Lassi Lehto, Jaakko Kahkonen, Juha Oksanen, Tapani Sarjakoski

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The use of raster-formatted data sets in geospatial analysis is increasing rapidly. At the same time, geographic data are being introduced into disciplines outside the traditional domain of geoinformatics, like climate change, intelligent transport, and immigration studies. These developments call for better methods to deliver raster geodata in an efficient and easy-to-use manner. Data cube technologies have traditionally been used in the geospatial domain for managing Earth Observation data sets that have strict requirements for effective handling of time series. The same approach and methodologies can also be applied in managing other types of geospatial data sets. A cloud service-based geodata cube, called GeoCubes Finland, has been developed to support online delivery and analysis of most important geospatial data sets with national coverage. The main target group of the service is the academic research institutes in the country. The most significant aspects of the GeoCubes data repository include the use of multiple resolution levels, cloud-optimized file structure, and a customized, flexible content access API. Input data sets are pre-processed while being ingested into the repository to bring them into a harmonized form in aspects like georeferencing, sampling resolutions, spatial subdivision, and value encoding. All the resolution levels are created using an appropriate generalization method, selected depending on the nature of the source data set. Multiple pre-processed resolutions enable new kinds of online analysis approaches to be introduced. Analysis processes based on interactive visual exploration can be effectively carried out, as the level of resolution most close to the visual scale can always be used. In the same way, statistical analysis can be carried out on resolution levels that best reflect the scale of the phenomenon being studied. Access times remain close to constant, independent of the scale applied in the application. The cloud service-based approach, applied in the GeoCubes Finland repository, enables analysis operations to be performed on the server platform, thus making high-performance computing facilities easily accessible. The developed GeoCubes API supports this kind of approach for online analysis. The use of cloud-optimized file structures in data storage enables the fast extraction of subareas. The access API allows for the use of vector-formatted administrative areas and user-defined polygons as definitions of subareas for data retrieval. Administrative areas of the country in four levels are available readily from the GeoCubes platform. In addition to direct delivery of raster data, the service also supports the so-called virtual file format, in which only a small text file is first downloaded. The text file contains links to the raster content on the service platform. The actual raster data is downloaded on demand, from the spatial area and resolution level required in each stage of the application. By the geodata cube approach, pre-harmonized geospatial data sets are made accessible to new categories of inexperienced users in an easy-to-use manner. At the same time, the multiresolution nature of the GeoCubes repository facilitates expert users to introduce new kinds of interactive online analysis operations.

Keywords: cloud service, geodata cube, multiresolution, raster geodata

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Authors: Shereen Kamel

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This study explores the recent application of bilingual education in Egyptian public schools. It aims to provide an overall picture of bilingual education programs globally and examine its adequacy to the Egyptian social and cultural context. The study also assesses the current application process of teaching English as a Second Language in public schools from the early childhood education stage and onwards, instead of starting it from middle school; as a strategy that promotes English language proficiency and equity among students. The theoretical framework is based on Jim Cummins’ bilingual education theories and on recent trends adopting different developmental theories and perspectives, like Stephen Crashen’s theory of Second Language Acquisition that calls for communicative and meaningful interaction rather than memorization of grammatical rules. The question posed here is whether bilingual education, with its peculiar nature, could be a good chance to reach out to all Egyptian students and prepare them to become global citizens. In addition to this, a more specific question is related to the extent to which social and cultural variables can affect the young learners’ second language acquisition. This exploratory analytical study uses mixed-methods research design to examine the application of bilingual education in Egyptian public schools. The study uses a cluster sample of schools in Egypt from different social and cultural backgrounds to assess the determining variables. The qualitative emphasis is on interviewing teachers and reviewing students’ achievement documents. The quantitative aspect is based on observations of in-class activities through tally sheets and checklists. Having access to schools and documents is authorized by governmental and institutional research bodies. Data sources will comprise achievement records, students’ portfolios, parents’ feedback and teachers’ viewpoints. Triangulation and SPSS will be used for analysis. Based on the gathered data, new curricula have been assigned for elementary grades and teachers have been required to teach the newly developed materials all of a sudden without any prior training. Due to shortage in the teaching force, many assigned teachers have not been proficient in the English language. Hence, teachers’ incompetency and unpreparedness to teach this grade specific curriculum constitute a great challenge in the implementation phase. Nevertheless, the young learners themselves as well as their parents seem to be enthusiastic about the idea itself. According to the findings of this research study, teaching English as a Second Language to children in public schools can be applicable and is culturally relevant to the Egyptian context. However, there might be some social and cultural differences and constraints when it comes to application in addition to various aspects regarding teacher preparation. Therefore, a new mechanism should be incorporated to overcome these challenges for better results. Moreover, a new paradigm shift in these teacher development programs is direly needed. Furthermore, ongoing support and follow up are crucial to help both teachers and students realize the desired outcomes.

Keywords: bilingual education, communicative approach, early childhood education, language and culture, second language acquisition

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Authors: S. Lahijanian, M. Mobli, B. Baninasab, N. Etemadi

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Low temperature extremes are amongst the major stresses that adversely affect the plant growth and productivity. Cold stress causes oxidative stress, physiological, morphological and biochemical changes in plant cells. Generally, low temperatures similar to salinity and drought exert their negative effects mainly by disrupting the ionic and osmotic equilibrium of the plant cells. Changes in climatic condition leading to more frequent extreme conditions will require adapted crop species on a larger scale in order to sustain agricultural production. Eucalyptus is a diverse genus of flowering trees (and a few shrubs) in the myrtle family, Myrtaceae. Members of this genus dominate the tree flora of Australia. The eucalyptus genus contains more than 580 species and large number of cultivars, which are native to Australia. Large distribution and diversity of compatible eucalyptus cultivars reflect the fact of ecological flexibility of eucalyptus. Some eucalyptus cultivars can sustain hard environmental conditions like high and low temperature, salinity, high level of PH, drought, chilling and freezing which are intensively effective on crops with tropical and subtropical origin. In this study, we tried to evaluate freezing tolerance of 12 eucalyptus genotypes by means of four different morphological and physiological methods: Chlorophyll fluorescence, electrolyte leakage, proline and stomatal density. The studied cultivars include Eucalyptus camaldulensis, E. coccifera, E. darlympleana, E. erythrocorys, E. glaucescens, E. globulus, E. gunnii, E. macrocorpa, E. microtheca, E. rubida, E. tereticornis, and E. urnigera. Except for stomatal density recording, in other methods, plants were exposed to five gradual temperature drops: zero, -5, -10, -15 and -20 degree of centigrade and they remained in these temperatures for at least one hour. Experiment for measuring chlorophyll fluorescence showed that genotypes E. erythrocorys and E. camaldulensis were the most resistant genotypes and E. gunnii and E.coccifera were more sensitive than other genotypes to freezing stress effects. In electrolyte leakage experiment with regard to significant interaction between cultivar and temperature, genotypes E. erythrocorys and E.macrocorpa were shown to be the most tolerant genotypes and E. gunnii, E. urnigera, E. microtheca and E. tereticornis with the more ionic leakage percentage showed to be more sensitive to low temperatures. Results of Proline experiment approved that the most resistant genotype to freezing stress is E. erythrocorys. In the stomatal density experiment, the numbers of stomata under microscopic field were totally counted and the results showed that the E. erythrocorys and E. macrocorpa genotypes had the maximum and E. coccifera and E. darlympleana genotypes had minimum number of stomata under microscopic field (0.0605 mm2). In conclusion, E. erythrocorys identified as the most tolerant genotype; meanwhile E. gunnii classified as the most freezing susceptible genotype in this investigation. Further, remarkable correlation was not obtained between the stomatal density and other cold stress measures.

Keywords: chlorophyll fluorescence, cold stress, ionic leakage, proline, stomatal density

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Authors: Utkarsh A. Mishra, Ankit Bansal

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At high temperature, radiative heat transfer is the dominant mode of heat transfer. It is governed by various phenomena such as photon emission, absorption, and scattering. The solution of the governing integrodifferential equation of radiative transfer is a complex process, more when the effect of participating medium and wavelength properties are taken into consideration. Although a generic formulation of such radiative transport problem can be modeled for a wide variety of problems with non-gray, non-diffusive surfaces, there is always a trade-off between simplicity and accuracy of the problem. Recently, solutions of complicated mathematical problems with statistical methods based on randomization of naturally occurring phenomena have gained significant importance. Photon bundles with discrete energy can be replicated with random numbers describing the emission, absorption, and scattering processes. Photon Monte Carlo (PMC) is a simple, yet powerful technique, to solve radiative transfer problems in complicated geometries with arbitrary participating medium. The method, on the one hand, increases the accuracy of estimation, and on the other hand, increases the computational cost. The participating media -generally a gas, such as CO₂, CO, and H₂O- present complex emission and absorption spectra. To model the emission/absorption accurately with random numbers requires a weighted sampling as different sections of the spectrum carries different importance. Importance sampling (IS) was implemented to sample random photon of arbitrary wavelength, and the sampled data provided unbiased training of MC estimators for better results. A better replacement to uniform random numbers is using deterministic, quasi-random sequences. Halton, Sobol, and Faure Low-Discrepancy Sequences are used in this study. They possess better space-filling performance than the uniform random number generator and gives rise to a low variance, stable Quasi-Monte Carlo (QMC) estimators with faster convergence. An optimal supervised learning scheme was further considered to reduce the computation costs of the PMC simulation. A one-dimensional plane-parallel slab problem with participating media was formulated. The history of some randomly sampled photon bundles is recorded to train an Artificial Neural Network (ANN), back-propagation model. The flux was calculated using the standard quasi PMC and was considered to be the training target. Results obtained with the proposed model for the one-dimensional problem are compared with the exact analytical and PMC model with the Line by Line (LBL) spectral model. The approximate variance obtained was around 3.14%. Results were analyzed with respect to time and the total flux in both cases. A significant reduction in variance as well a faster rate of convergence was observed in the case of the QMC method over the standard PMC method. However, the results obtained with the ANN method resulted in greater variance (around 25-28%) as compared to the other cases. There is a great scope of machine learning models to help in further reduction of computation cost once trained successfully. Multiple ways of selecting the input data as well as various architectures will be tried such that the concerned environment can be fully addressed to the ANN model. Better results can be achieved in this unexplored domain.

Keywords: radiative heat transfer, Monte Carlo Method, pseudo-random numbers, low discrepancy sequences, artificial neural networks

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Authors: Alastair Hales, Xi Jiang, Siming Zhang

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Numerical methods are used to generate vortices in a domain. Through considered design, two counter-rotating vortices may interact and effectively drive one another downstream. This phenomenon is comparable to the vortex interaction that occurs in a region immediately downstream from two counter-oscillating piezoelectric (PE) fan blades. PE fans are small blades clamped at one end and driven to oscillate at their first natural frequency by an extremely low powered actuator. In operation, the high oscillation amplitude and frequency generate sufficient blade tip speed through the surrounding air to create downstream air flow. PE fans are considered an ideal solution for low power hot spot cooling in a range of small electronic devices, but a single blade does not typically induce enough air flow to be considered a direct alternative to conventional air movers, such as axial fans. The development of face-to-face PE fan arrays containing multiple blades oscillating in counter-phase to one another is essential for expanding the range of potential PE fan applications regarding the cooling of power electronics. Even in an unoptimised state, these arrays are capable of moving air volumes comparable to axial fans with less than 50% of the power demand. Replicating the airflow generated by face-to-face PE fan arrays without including the actual blades in the model reduces the process’s computational demands and enhances the rate of innovation and development in the field. Vortices are generated at a defined inlet using a time-dependent velocity profile function, which pulsates the inlet air velocity magnitude. This induces vortex generation in the considered domain, and these vortices are shown to separate and propagate downstream in a regular manner. The generation and propagation of a single vortex are compared to an equivalent vortex generated from a PE fan blade in a previous experimental investigation. Vortex separation is found to be accurately replicated in the present numerical model. Additionally, the downstream trajectory of the vortices’ centres vary by just 10.5%, and size and strength of the vortices differ by a maximum of 10.6%. Through non-dimensionalisation, the numerical method is shown to be valid for PE fan blades with differing parameters to the specific case investigated. The thorough validation methods presented verify that the numerical model may be used to replicate vortex formation from an oscillating PE fans blade. An investigation is carried out to evaluate the effects of varying the distance between two PE fan blade, pitch. At small pitch, the vorticity in the domain is maximised, along with turbulence in the near vicinity of the inlet zones. It is proposed that face-to-face PE fan arrays, oscillating in counter-phase, should have a minimal pitch to optimally cool nearby heat sources. On the other hand, downstream airflow is maximised at a larger pitch, where the vortices can fully form and effectively drive one another downstream. As such, this should be implemented when bulk airflow generation is the desired result.

Keywords: piezoelectric fans, low energy cooling, vortex formation, computational fluid dynamics

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

Procedia PDF Downloads 326

Authors: Suneet Jagdev, Hrishabh Amrodia, Siddharth Menon, Abhishek Singh, Mansi Shivhare

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Delhi, the National Capital, has undergone a surge in development rate, consequently engendering an unprecedented increase in population. Over the years the city has transformed into a car-centric infrastructure with high-speed corridors, flyovers and fast lanes. A considerable section of the population is hankering to rehabilitate to the good old cycling days, in order to contribute towards a green environment as well as to maintain their physical well-being. Furthermore, an extant section of Delhi’s population relies on cycles as their primary means of commuting in the city. Delhi has the highest number of cyclists and second highest number of pedestrians in the country. However, the tumultuous problems of unregulated traffic, inadequate space on roads, adverse weather conditions stifle them to opt for cycling. Lately, the city has been facing a conglomeration of problems such as haphazard traffic movement, clogged roads, congestion, pollution, accidents, safety issues, etc. In 1957, Delhi’s cyclists accounted for 36 per cent of trips which dropped down to a mere 4 per cent in 2008. The declining rate is due to unsafe roads and lack of proper cycle lanes. Now as the 10 percent of the city has cycle tracks. There is also a lack of public recreational activities in the city. These conundrums incite the need of a covered elevated cycling bridge track to facilitate the safe and smooth cycle commutation in the city which would also serve the purpose of an alternate urban public space over the cycle bridge reducing the cost as well as the space requirement for the same, developing a user–friendly transportation and public interaction system for urban areas in the city. Based on the archival research methodologies, the following research draws information and extracts records from the data accounts of the Delhi Metro Rail Corporation Ltd. as well as the Centre for Science and Environment, India. This research will predominantly focus on developing a prototype design for high speed elevated bicycle lanes based on different road typologies, which can be replicated with minor variations in similar situations, all across the major cities of our country including the proposed smart cities. Furthermore, how these cycling lanes could be utilized for the place making process accommodating cycle parking and renting spaces, public recreational spaces, food courts as well as convenient shopping facilities with appropriate optimization. How to preserve and increase the share of smooth and safe cycling commute cycling for the routine transportation of the urban community of the polluted capital which has been on a steady decline over the past few decades.

Keywords: bicycle track, prototype, road safety, urban spaces

Procedia PDF Downloads 130

Authors: T. Santiboon, S. Tongbu, P. S. Saihong

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This study focuses on investigating students' perceptions of their physics classroom learning environments of their individualizations and their interactions with the instructional practicum in teaching physics of the master science trainee educational students for improving and creating attitude skills’ sustainable development toward physics for upper secondary educational students in Thailand. Associations between these perceptions and students' attitudes toward physics were also determined. The learning environment perceptions were obtained using the 35-item Physics Laboratory Environment Inventory (PLEI) modified from the original Science Laboratory Environment Inventory. The 25-item Individualized Classroom Environment Questionnaire (ICEQ) was assessed those dimensions which distinguish individualized physics classrooms from convention on individualized open and inquiry-based education Teacher-student interactions were assessed with the 48-item Questionnaires on Teacher Interaction (QTI). Both these questionnaires have an Actual Form (assesses the class as it actually is) and a Preferred Form (asks the students what they would prefer their class to be like - the ideal situation). Students’ creating attitude skills’ sustainable development toward physics were assessed with the Test Of Physics-Related Attitude (TOPRA) modified from the original Test Of Science-Related Attitude (TOSRA) The questionnaires were administered in three phases with the Custer Random Sampling technique to a sample consisted of 989 students in 28 physics classes from 10 schools at the grade 10, 11, and 12 levels in the Secondary Educational Service Area 26 (Maha Sarakham Province) and Area 27 (Roi-Et). Statistically significant differences were found between the students' perceptions of actual-1, actual-2 and preferred environments of their physics laboratory and distinguish individualized classrooms, and teacher interpersonal behaviors with their improving and creating attitudes skills’ sustainable development to their physics classes also were found. Predictions of the monitoring and evaluation of master science trainee educational students of their practicum in teaching physics; students’ skills developments of their physics achievements’ sustainable for the set of actual and preferred environments as a whole and physics related attitudes also were correlated. The R2 values indicate that 58%, 67%, and 84% of the variances in students’ attitudes to their actuale-1, actual-2 and preferred for the PLEI; 42%,science trainee educational students of their practicum in teaching physics; students’ skill developments of their physics achievements’ sustainable for the set of actual and preferred environments as a whole and physics related attitudes also were correlated. The R2 values indicate that 58%, 67%, and 84% of the variances in students’ attitudes to their actuale-1, actual-2 and preferred for the PLEI; 42%, 63%, and 72% for the ICEQ, and 38%, 59%, and 68% for the QTI in physics environment classes were attributable to their perceptions of their actual and preferred physics environments and their developing creative science skills’ sustainable toward physics, consequently. Based on all the findings, suggestions for improving the physics laboratory and individualized classes and teacher interpersonal behaviors with students' perceptions are provided of their improving and creating attitude skills’ sustainable development by the master science trainee educational students ’ instructional administrations.

Keywords: promotion, instructional model, qualitative method, reflective thinking, trainee teacher student

Procedia PDF Downloads 239

Authors: Sumedha Weerasekara, Morgan Miles, Mark Morrison, Branka Krivokapic-Skoko

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This paper is aimed at exploring the interrelationships among entrepreneurial ecosystem factors and entrepreneurial cognition in regional and metropolitan ecosystems. Entrepreneurial ecosystem factors examined include: culture, infrastructure, access to finance, informal networks, support services, access to universities, and the depth and breadth of the talent pool. Using a multivariate approach we explore the impact of these ecosystem factors or elements on entrepreneurial cognition. In doing so, the existing body of knowledge from the literature on entrepreneurial ecosystem and cognition have been blended to explore the relationship between entrepreneurial ecosystem factors and cognition in a way not hitherto investigated. The concept of the entrepreneurial ecosystem has received increased attention as governments, universities and communities have started to recognize the potential of integrated policies, structures, programs and processes that foster entrepreneurship activities by supporting innovation, productivity and employment growth. The notion of entrepreneurial ecosystems has evolved and grown with the advancement of theoretical research and empirical studies. Importance of incorporating external factors like culture, political environment, and the economic environment within a single framework will enhance the capacity of examining the whole systems functionality to better understand the interaction of the entrepreneurial actors and factors within a single framework. The literature on clusters underplays the role of entrepreneurs and entrepreneurial management in creating and co-creating organizations, markets, and supporting ecosystems. Entrepreneurs are only one actor following a limited set of roles and dependent upon many other factors to thrive. As a consequence, entrepreneurs and relevant authorities should be aware of the other actors and factors with which they engage and rely, and make strategic choices to achieve both self and also collective objectives. The study uses stratified random sampling method to collect survey data from 12 different regions in regional and metropolitan regions of NSW, Australia. A questionnaire was administered online among 512 Small and medium enterprise owners operating their business in selected 12 regions in NSW, Australia. Data were analyzed using descriptive analyzing techniques and partial least squares - structural equation modeling. The findings show that even though there is a significant relationship between each and every entrepreneurial ecosystem factors, there is a weak relationship between most entrepreneurial ecosystem factors and entrepreneurial cognition. In the metropolitan context, the availability of finance and informal networks have the largest impact on entrepreneurial cognition while culture, infrastructure, and support services having the smallest impact and the talent pool and universities having a moderate impact on entrepreneurial cognition. Interestingly, in a regional context, culture, availability of finance, and the talent pool have the highest impact on entrepreneurial cognition, while informal networks having the smallest impact and the remaining factors – infrastructure, universities, and support services have a moderate impact on entrepreneurial cognition. These findings suggest the need for a location-specific strategy for supporting the development of entrepreneurial cognition.

Keywords: academic achievement, colour response card, feedback

Procedia PDF Downloads 116

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

Procedia PDF Downloads 317