Search results for: mechanism/s of action

Authors: Sami Meddeb, M. L Giorgi, J. L. Courouau

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This work presents the progress of studies aiming to guarantee the lifetime of 316L(N) steel in a sodium-cooled fast reactor by determining the elementary corrosion mechanism, which is akin to an accelerated dissolution by dissolved oxygen. The mechanism involving iron, the main element of steel, is particularly studied in detail, from the viewpoint of the data available in the literature, the modeling of the various mechanisms hypothesized. Experiments performed in the CORRONa facility at controlled temperature and dissolved oxygen content are used to test both literature data and hypotheses. Current tests, performed at various temperatures and oxygen content, focus on specifying the chemical reaction at play, determining its free enthalpy, as well as kinetics rate constants. Specific test configuration allows measuring the reaction kinetics and the chemical equilibrium state in the same test. In the current state of progress of these tests, the dissolution of iron accelerated by dissolved oxygen appears as directly related to a chemical complexation reaction of mixed iron-sodium oxide (Na-Fe-O), a compound that is soluble in the liquid sodium solution. Results obtained demonstrate the presence in the solution of this corrosion product, whose kinetics is the limiting step under the conditions of the test. This compound, the object of hypotheses dating back more than 50 years, is predominant in solution compared to atomic iron, presumably even for the low oxygen concentration, and cannot be neglected for the long-term corrosion modeling of any heat transfer system.

Keywords: corrosion, sodium fast reactors, iron, oxygen

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Authors: Ulysse Lecomte, Maryline Thenot

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For a long time, disabled people lived in isolation within the family environment, with little interaction with the outside world and a high risk of social exclusion. However, in a number of countries, progress has been made thanks to changes in legislation on the social integration of disabled people, a significant change in attitudes, and the development of CSR. But the problem of their social, economic, and professional exclusion persists and has been further exacerbated by the COVID-19 pandemic. This societal phenomenon is sufficiently important to be the subject of management science research. We have therefore focused our work on society's current perception of people with disabilities and their possible integration. Our aim is to find out what levers could be put in place to bring about positive change in the situation. We have chosen to focus on the perception of young people in France, who are the new generation responsible for the future of our society and from whom tomorrow's decisionmakers, future employers, and stakeholders who can influence the living conditions of disabled people will be drawn. Our study sample corresponds to the 18-30 age group, which is the population of young adults likely to have sufficient experience and maturity. The aim of this study is not only to find out how this population currently perceives disability but also to identify the factors influencing this perception and the most effective levers for action to act positively on this phenomenon and thus promote better social integration of people with disabilities in the future. The methodology is based on theoretical and empirical research. The literature review includes a historical and etymological approach to disability, a definition of the different concepts of disability, an approach to disability as a vector of social exclusion, and the role of perception and representations in defining the social image of disability. This literature review is followed by an empirical part carried out by means of a questionnaire administered to 110 young people aged 18 to 30. Analysis of our results suggests that, despite a recent improvement, disabled people are still perceived as vulnerable and socially marginalised. The following factors stand out as having a significant influence (positive or negative) on the perception of disability: the individual's familiarity with the 'world of disability', cultural factors, the degree of 'visibility' of the disability and the empathy level of the disabled person him/herself. Others, on the other hand, such as socio-political and economic factors, have little impact on this perception. In addition, it is possible to classify the various levers of action likely to improve the social perception of disability according to their degree of effectiveness. Our study population prioritised training initiatives for the various players and stakeholders (teachers, students, disabled people themselves, companies, sports clubs, etc.). This was followed by communication, ecommunication and media campaigns in favour of disability. Lastly, the sample was judged as 'less effective' positive discrimination actions such as setting a minimum percentage for the representation of disabled people in various fields (studies, employment, politics ...).

Keywords: disability, perception, social image, young people, influencing factors, levers for action

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Authors: Nuhu Mohammed Gali, Kenichi Matsui

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Climate change poses a significant threat to agriculture and food security in Africa. The UNFCC recognized the need to address climate change adaptation in the broader context of sustainable development. African countries have initiated a governance system for adapting and responding to climate change in their Nationally Determined Contributions (NDCs). Despite the implementation limitations, Africa’s adaptation initiatives highlight the need to strengthen and expand adaptation responses. This paper looks at the extent to which South-South cooperation facilitates the implementation of adaptation actions between nations for agriculture and sustainable development. We conducted a literature review and content analysis of reports prepared by international organizations, reflecting the diversity of adaptation activities taking place in Sub-Saharan Africa. Our analysis of the connection between adaptation and nationally determined contributions (NDCs) showed that climate actions are mainstreamed into sustainable development. The NDCs in many countries on climate change adaptation action for agriculture aimed to strengthen the resilience of the poor. We found that climate-smart agriculture is the core of many countries target to end hunger. We revealed that South-South Cooperation, in terms of capacity, technology, and financial support, can help countries to achieve their climate action priorities and the Sustainable Development Goals (SDGs). We found that inadequate policy and regulatory frameworks between countries, differences in development priorities and strategies, poor communication, inadequate coordination, and the lack of local engagement and advocacy are some key barriers to South-South Cooperation in Africa. We recommend a multi-dimensional partnership, provisionoffinancialresources, systemic approach for coordination and engagement to promote and achieve the potential of SSC in Africa.

Keywords: climate change, adaptation, food security, sustainable development goals

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Authors: Esmaeil Asadzadeh, Mehtab Alam

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Well documented records of the past failures of the structures reveals that the progressive collapse of structures is one of the major reasons for dramatic human loss and economical consequences. Progressive collapse is the failure mechanism in which the structure fails gradually due to the sudden removal of the structural elements. The sudden removal of some structural elements results in the excessive redistributed loads on the others. This sudden removal may be caused by any sudden loading resulted from local explosion, impact loading and terrorist attacks. Hyperbolic thin walled concrete shell structures being an important part of nuclear and thermal power plants are always prone to such terrorist attacks. In concrete structures, the gradual failure would take place by generation of initial cracks and its propagation in the supporting columns along with the tower shell leading to the collapse of the entire structure. In this study the mechanism of progressive collapse for such high raised towers would be simulated employing the finite element method. The aim of this study would be providing clear conceptual step-by-step descriptions of various procedures for progressive collapse analysis using commercially available finite element structural analysis software’s, with the aim that the explanations would be clear enough that they will be readily understandable and will be used by practicing engineers. The study would be carried out in the following procedures: 1. Provide explanations of modeling, simulation and analysis procedures including input screen snapshots; 2. Interpretation of the results and discussions; 3. Conclusions and recommendations.

Keywords: progressive collapse, cooling towers, finite element analysis, crack generation, reinforced concrete

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Authors: Ribut Alam Malau, Durri Andriani, C. B. Supartomo

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Universitas Terbuka (UT) as a higher education institution implements open and distance education is responsible to provide higher education to all Indonesian citizen wherever they live, including those reside in cultural diversity aras. Operate from Jakarta Head Office and 37 regional centers (ROs), UT is accustomed to the challenge. UT-Kupang and UT-Ambon which oversee East Nusa Tenggara and Maluku have successfully provided quality educational services for students. The two ROs have provided educational facilities which could assist the students to cope with their study in spite of the diversity situations. In order to analyze the effectiveness of the facilities provided, questionnaires focusing on tutorial services were sent to 90 students in the two ROs asking them to assess the facilities which best fulfills students’ needs in terms of their culture diversity. The results showed that UT-Kupang and UT-Ambon have successful in providing education for students in their areas as reflected in more than 80% of respondents aware of the facilities concerning tutorial service except for tutorial mechanism where only 34,5% of respondents aware of. However, despite lower rate of awareness in tutorial mechanism, majority of respondent 90.8% of respondents registered in tutorials and 95.4% will register in tutorials next semester. The majority of respondents showed appreciation for the ROs efforts to provide tutorials on weekdays which could accommodate their beliefs. In addition, conducting tutorials in all islands also perceived highly since students did not have to commute between islands. Efforts done by UT-Kupang and UT-Ambon have proven to be appreciated by students.

Keywords: archipelago, cultural diversity, ODL, service quality, Universitas Terbuka

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Authors: Moulay Driss Mellaoui, Abdallah Imjjad, Rachid Boutiddar, Haydar Mohammad-Salim, Nivedita Acharjee, Hassan Bourzi, Souad El Issami, Khalid Abbiche, Hanane Zejli

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We have investigated the underlying molecular processes involved in the [3+2] cycloaddition (32CA) reactions between N-methyl-C-(2-furyl) nitrone and three acetylene derivatives: 4b, 5b, and 6b. For this investigation, we utilized molecular electron density theory (MEDT) and density functional theory (DFT) methods at the B3LYP-D3/6 31G (d) computational level. These 32CA reactions, which exhibit a zwitterionic (zw-type) nature, proceed through a one-step mechanism with activation enthalpies ranging from 8.80 to 14.37 kcal mol−1 in acetonitrile and ethanol solvents. When the nitrone reacts with phenyl methyl propiolate (4b), two regioisomeric pathways lead to the formation of two products: P1,5-4b and P1,4-4b. On the other hand, when the nitrone reacts with dimethyl acetylene dicarboxylate (5b) and acetylene dicarboxylic acid (but-2-ynedioic acid) (6b), it results in the formation of a single product. Through topological analysis, we can categorize the nitrone as a zwitterionic three-atom component (TAC). Furthermore, the analysis of conceptual density functional theory (CDFT) indices classifies the 32CA reactions of the nitrone with 4b, 5b, and 6b as forward electron density flux (FEDF) reactions. The study of bond evolution theory (BET) reveals that the formation of new C-C and C-O covalent bonds does not initiate in the transition states, as the intermediate stages of these reactions display pseudoradical centers of the atoms already involved in bonding.

Keywords: 4-isoxazoline, DFT/B3LYP-D3, regioselectivity, cycloaddition reaction, MEDT, ELF

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Authors: Malkhaz Jokhadze, Vakhtang Mshvildadze, Levan Makaradze, Ekaterine Mosidze, Salome Barbaqadze, Mariam Murtazashvili, Dali Berashvili, Koba sivsivadze, Lasha Bakuridze, Aliosha Bakuridze

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Essential oils are one of the most important groups of biologically active substances present in plants. Due to the chemical diversity of components, essential oils and their preparations have a wide spectrum of pharmacological action. They have bactericidal, antiviral, fungicidal, antiprotozoal, anti-inflammatory, spasmolytic, sedative and other activities. They are expectorant, spasmolytic, sedative, hypotensive, secretion enhancing, antioxidant remedies. Based on preliminary pharmacological studies, we have developed a formulation called “Phytobiotic” containing essential oils, a feed additive for poultry as an alternative to antibiotics. Phytobiotic is a water-soluble powder containing a composition of essential oils of thyme, clary, monarda and auxiliary substances: dry extract of liquorice and inhalation lactose. On this stage of research, the goal was to study the chemical composition of provided phytobiotic, identify the main substances and determine their quantity, investigate the biological activity of phytobiotic through in vitro and in vivo studies. Using gas chromatography-mass spectrometry, 38 components were identified in phytobiotic, representing acyclic-, monocyclic-, bicyclic-, and sesquiterpenes. Together with identification of main active substances, their quantitative content was determined, including acyclic terpene alcohol β-linalool, acyclic terpene ketone linalyl acetate, monocyclic terpenes: D-limonene and γ-terpinene, monocyclic aromatic terpene thymol. Provided phytobiotic has pronounced and at the same time broad spectrum of antibacterial activity. In the cell model, phytobiotic showed weak antioxidant activity, and it was stronger in the ORAC (chemical model) tests. Meanwhile anti-inflammatory activity was also observed. When fowls were supplied feed enriched with phytobiotic, it was observed that gained weight of the chickens in the experimental group exceeded the same data for the control group during the entire period of the experiment. The survival rate of broilers in the experimental group during the growth period was 98% compared to -94% in the control group. As a result of conducted researches probable four different mechanisms which are important for the action of phytobiotics were identified: sensory, metabolic, antioxidant and antibacterial action. General toxic, possible local irritant and allergenic effects of phytobiotic were also investigated. Performed assays proved that formulation is safe.

Keywords: clary, essential oils, monarda, poultry, phytobiotics, thyme

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Authors: Huayuan Lu, Chunfang Yang, Ma Zhu, Baojun Qi, Yaqiong Qiao, Jiangqian Xu

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Image geolocalization has great application prospects in fields such as autonomous driving and virtual/augmented reality. In practical application scenarios, the size of the image to be located is not fixed; it is impractical to train different networks for all possible sizes. When its size does not match the size of the input of the descriptor extraction model, existing image geolocalization methods usually directly scale or crop the image in some common ways. This will result in the loss of some information important to the geolocalization task, thus affecting the performance of the image geolocalization method. For example, excessive down-sampling can lead to blurred building contour, and inappropriate cropping can lead to the loss of key semantic elements, resulting in incorrect geolocation results. To address this problem, this paper designs a learnable image resizer and proposes an arbitrary-sized image geolocation method. (1) The designed learnable image resizer employs the self-attention mechanism to enhance the geometric features of the resized image. Firstly, it applies bilinear interpolation to the input image and its feature maps to obtain the initial resized image and the resized feature maps. Then, SKNet (selective kernel net) is used to approximate the best receptive field, thus keeping the geometric shapes as the original image. And SENet (squeeze and extraction net) is used to automatically select the feature maps with strong contour information, enhancing the geometric features. Finally, the enhanced geometric features are fused with the initial resized image, to obtain the final resized images. (2) The proposed image geolocalization method embeds the above image resizer as a fronting layer of the descriptor extraction network. It not only enables the network to be compatible with arbitrary-sized input images but also enhances the geometric features that are crucial to the image geolocalization task. Moreover, the triplet attention mechanism is added after the first convolutional layer of the backbone network to optimize the utilization of geometric elements extracted by the first convolutional layer. Finally, the local features extracted by the backbone network are aggregated to form image descriptors for image geolocalization. The proposed method was evaluated on several mainstream datasets, such as Pittsburgh30K, Tokyo24/7, and Places365. The results show that the proposed method has excellent size compatibility and compares favorably to recently mainstream geolocalization methods.

Keywords: image geolocalization, self-attention mechanism, image resizer, geometric feature

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Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

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Authors: T. Aragaw, P. Gari

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In spite of social, political, and economic marginalization, women are still considered as the backbone of Ethiopia, one of the least developed countries in the world. The general purpose of this study was to assess factors that affect participation of women in politics, social and economic decisions at Kelem-Wollega Administrative Zone of Oromia Regional State, Ethiopia. Data used in this paper is mainly primary, and a few secondary data were incorporated. Respondents were selected using a systematic random sampling method and were placed questionnaires containing open-ended and closed-ended. Focus group discussion was also used for the study subjects in two offices. According to the information collected from the KWAZ Development and Social Service Office, a total of 18,473 tax-paying employees are present in the Zone, which is 14% of the total population of the Zone. Among the total number of employees in the Zone, 2,617 have been recruited for this study based on the criteria stated. This showed 1.8% of them were comprised of several churches and religious owned integrated development projects in the KWAZ. The 2,103 (80.34%) study participants responded personally, and they completed and returned the questionnaire to the researchers. The study revealed that in public institutions existed in KWAZ, the majority of women were having an educational status of diploma and lower, practicing lower non-decision making and leadership positions. Conclusion: Major barriers hindering women include: Socio-cultural attitudes, lack of necessary experience, education, the burden of domestic responsibilities, and lack of role models of women leaders in the Zone. Empowerment of women via social organizations, critical involvement of the government, and Affirmative action for women is critical. Further research is needed on the scope and challenges in implementing the strategies.

Keywords: women, affirmative action, leadership, empowerment, Ethiopia

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Authors: Wan Jen Chang

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Back ground: Taiwan's current adult lifelong learning services have expanded from vocational training to universal lifelong learning. However, both the professional knowledge training of learning guidance and consulting services and the provision of adult online learning consulting service systems still need to be established. Purpose: The purposes of this study are as follows: 1. Analyze the professional training mechanism for cultivating adult lifelong learning consultation and coaching; 2. Explore the feasibility of constructing a system that uses network technology to provide adult learning consultation services. Research design: This study conducts a literature analysis of counseling and coaching policy reports on lifelong learning in European countries and the United States. There are two focus discussions were conducted with 15 lifelong learning scholars, experts and practitioners as research subjects. The following two topics were discussed and suggested: 1. The current situation, needs and professional ability training mechanism of "Adult Lifelong Learning Consulting and Services"; 2. Strategies for establishing an "Adult Lifelong Learning Consulting and Service internet System". Conclusion: 1.Based on adult lifelong learning consulting and service needs, plan a professional knowledge training and certification system.2.Adult lifelong learning consulting and service professional knowledge and skills training should include the use of network technology to provide consulting service skills.3.To establish an adult lifelong learning consultation and service system, the Ministry of Education should promulgate policies and measures at the central level and entrust local governments or private organizations to implement them.4.The adult lifelong learning consulting and service system can combine the national qualifications framework, private sector and NPO to expand learning consulting service partners.

Keywords: adult lifelong learning, profesional knowledge, consulting and service, network system

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Authors: Miky Lee, K. Kim, D. Lim, D. Cho

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This paper presents the planning, rationale for test specification derivation, sampling requirements, test facilities, and result analysis used to conduct lifetime expectancy endurance tests on power window switches (PWS) considering thermally induced mechanical stress under diurnal cyclic temperatures during normal operation (power cycling). The detail process of analysis and test results on the selected PWS set were discussed in this paper. A statistical approach to ‘life time expectancy’ was given to the measurement standards dealing with PWS lifetime determination through endurance tests. The approach choice, within the framework of the task, was explained. The present task was dedicated to voltage drop measurement to derive lifetime expectancy while others mostly consider contact or surface resistance. The measurements to perform and the main instruments to measure were fully described accordingly. The failure data from tests were analyzed to conclude lifetime expectancy through statistical method using Weibull cumulative distribution function. The first goal of this task is to develop realistic worst case lifetime endurance test specification because existing large number of switch test standards cannot induce degradation mechanism which makes the switches less reliable. 2nd goal is to assess quantitative reliability status of PWS currently manufactured based on test specification newly developed thru this project. The last and most important goal is to satisfy customer’ requirement regarding product reliability.

Keywords: power window switch, endurance test, Weibull function, reliability, degradation mechanism

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Authors: M.A. Ali, M. Matloob, A. Sahar, M. Yamin, M. Imran, Y.A. Yusof

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Quinoa (Chenopodium quinoa Willd.) is known as pseudocereal was originated in South America's Andes. Quinoa is a good source of protein, amino acids, micronutrients and bioactive components. The lack of gluten makes it suitable for celiac patients. Saponins, the leading ant-nutrient, are found in the pericarp, which adheres to the seed and transmits the bitter flavor to the quinoa grain. It is found in varying amounts in quinoa from 0.1% to 5%. This study was planned to design an indigenous machine to remove saponin from quinoa grains at the farm level to promote entrepreneurship. The machine consisted of a feeding hopper, rotating shaft, grooved stone, perforated steel cylinder, V-belts, pulleys, electric motor and mild steel angle iron and sheets. The motor transmitted power to the shaft with a belt drive. The shaft on which the grooved stone was attached rotated inside the perforated cylinder having a clearance of 2 mm and was removed saponin by an abrasion mechanism. The saponin-removed quinoa was then dipped in water to determine the presence of saponin as it produced foam in water and data were statistically analyzed. The results showed that the raw seed feeding rate of 25 g/s and milling time of 135 s completely removed saponin from seeds with minimum grain losses of 2.85% as compared to the economic analysis of the machine showed that its break-even point was achieved after one and half months with 18,000 s and a production capacity of 33 g/s.

Keywords: quinoa seeds, saponin, abrasion mechanism, stone polishing, indigenous machine

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Authors: B. S. Yadav, A. Mani, S. Srivastava

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Chickpea (Cicer arietinum L.) is an annual, self-pollinating, diploid (2n = 2x = 16) pulse crop that ranks second in world legume production after common bean (Phaseolus vulgaris). ICC 4958 flowers approximately 39 days after sowing under peninsular Indian conditions and the crop matures in less than 90 days in rained environments. The estimated collective yield losses due to abiotic stresses (6.4 million t) have been significantly higher than for biotic stresses (4.8 million t). Most legumes are known to be salt sensitive, and therefore, it is becoming increasingly important to produce cultivars tolerant to high-salinity in addition to other abiotic and biotic stresses for sustainable chickpea production. Our aim was to identify the genes that are involved in the defence mechanism against heavy metal toxicity in chickpea and establish the biological network of heavy metal toxicity in chickpea. ICC4958 variety of chick pea was taken and grown in normal condition and 150µM concentration of different heavy metal salt like CdCl₂, K₂Cr2O₇, NaAsO₂. At 15th day leave samples were collected and stored in RNA Later solution microarray was performed for checking out differential gene expression pattern. Our studies revealed that 111 common genes that involved in defense mechanism were up regulated and 41 genes were commonly down regulated during treatment of 150µM concentration of CdCl₂, K₂Cr₂O₇, and NaAsO₂. Biological network study shows that the genes which are differentially expressed are highly connected and having high betweenness and centrality.

Keywords: abiotic stress, biological network, chickpea, microarray

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Authors: Roula Kitsiou, Sofia Tsioli, Eleni Gana

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

Keywords: blended learning, integration, language education, refugees

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Authors: Velázquez Alejandro, Pradhan Sujan, Yoon Rokhyun, Sanada Yasushi

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The utilization of new materials as an alternative solution to decrease the environmental impact of the construction industry has been gaining more relevance in the architectural design and construction industry. One such material is cross-laminated timber (CLT), an engineered timber solution that excels for its faster construction times, workability, lightweight, and capacity for carbon storage. This material is usually used alone for the entire structure or combined with steel frames, but a hybrid with reinforced concrete (RC) is rarer. Since RC is one of the most used materials worldwide, a hybrid with CLT would allow further utilization of the latter, and in the process, it would help reduce the environmental impact of RC construction to achieve a sustainable society, but first, the structural performance of such hybrids must be understood. This paper focuses on proposing a model to predict the seismic performance of RC frames with CLT panels as infills. A series of static horizontal cyclic loading experiments were conducted on two 40% scale specimens of reinforced concrete frames with and without CLT panels at Osaka University, Japan. An analytical model was created to simulate the seismic performance of the RC frame with CLT infill based on the experimental results. The proposed model was verified by comparing the experimental and analytical results, showing that the load-deformation relationship and the failure mechanism agreed well with limited error. Hence, the proposed analytical model can be implemented for the seismic performance evaluation of the RC frames with CLT infill.

Keywords: analytical model, multi spring, performance evaluation, reinforced concrete, rocking mechanism, wooden wall

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Authors: Yasam Palguna, Rajesh Korla

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The efficiency of thermally operated systems can be improved by increasing the operating temperature, thereby decreasing the fuel consumption and carbon footprint. Hence, there is a continuous need for replacing the existing materials with new alloys with higher temperature working capabilities. During the last decade, multi principal element alloys, commonly known as high entropy alloys are getting more attention because of their superior high temperature strength along with good high temperature corrosion and oxidation resistance, The present work focused on the microstructure and high temperature tensile behavior of Al0.2CoCrFeNiMo0.5 high entropy alloy (HEA). Wrought Al0.2CoCrFeNiMo0.5 high entropy alloy, produced by vacuum induction melting followed by thermomechanical processing, is tested in the temperature range of 200 to 900oC. It is exhibiting very good resistance to softening with increasing temperature up to 700oC, and thereafter there is a rapid decrease in the strength, especially beyond 800oC, which may be due to simultaneous occurrence of recrystallization and precipitate coarsening. Further, it is exhibiting superplastic kind of behavior with a uniform elongation of ~ 275 % at 900 oC temperature and 1 x 10-3 s-1 strain rate, which may be due to the presence of fine stable equi-axed grains. Strain rate sensitivity of 0.3 was observed, suggesting that solute drag dislocation glide might be the active mechanism during superplastic kind of deformation. Post deformation microstructure suggesting that cavitation at the sigma phase-matrix interface is the failure mechanism during high temperature deformation. Finally, high temperature properties of the present alloy will be compared with the contemporary high temperature materials such as ferritic, austenitic steels, and superalloys.

Keywords: high entropy alloy, high temperature deformation, super plasticity, post-deformation microstructures

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Authors: Gabriele Palumbo

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This research empirically examines some of the reasons behind the fact that recently the number of people giving up their American citizenship for tax purposes has recently increased drastically. The United States Jurisdiction represents a unicum in the practice of taxing worldwide income not only to residents of the United States but also to U.S. citizens living abroad. The worldwide income taxation also affects people defined as “Accidental Americans” who are unaware that they are U.S. citizens. Those people are considered Americans even though they have not been to the United States. American residents abroad can rely on United States income tax treaties and some national law provisions, such as the exclusion of foreign income and foreign tax credits, which are designed specifically to avoid double taxation. However, this mechanism may prove unsatisfactory for people who have not been linked anymore or individuals who have never had relations with the United States. U.S. citizens who are determined to cut all of the ties between themselves and the United States, especially those that involve tax implications, can renounce their U.S. citizenship with the expatriation procedure. The expatriation process represents the extrema ratio and implicates several steps which must be followed carefully. This paper shows the complexity of the procedure that a U.S. citizen who is resident in a foreign country would have to follow to relinquish U.S. citizenship for tax purposes. The mechanism is intended to discourage people from renounce. Going beyond the question of whether U.S. tax regulation is fair or not, this principle nowadays characterizes a popular topic that many scholars and lawyers are discussing. The outcome provides interesting implications that could induce the Congress to rethink the definition of citizenship for both fiscal and nationality law purposes. Indeed, even if a sort of checks and balances has the task of mitigating the renunciation of U.S. citizenship, more and more U.S. citizens desire to get rid of their citizenship.

Keywords: double taxation, expatriation tax, international taxation, relinquishment of United States citizenship

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Authors: Min-Feng Hsieh

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Nowadays, we are facing a highly competitive environment in which the situation for survival has come even more critical than ever before. The challenge we will be confronted with is no longer can be dealt with the single system of knowledge. The abilities we urgently need to acquire is something that can lead us to cross over the boundaries between different disciplines and take us to a neutral ground that gathers and integrates powers and intelligence that surrounds us. This paper aims at discussing how a trans-disciplinary design course organized by the College of Design at Chaoyang University can react to this modern challenge. By orchestrating an experimental course format and by developing a series of coaching strategies, a trans-disciplinary learning environment has been created and practiced in which students selected from five different departments, including Architecture, Interior Design, Visual Design, Industrial Design, Landscape and Urban Design, are encouraged to think outside their familiar knowledge pool and to learn with/from each other. In the course of implementing this program, a parallel research has been conducted alongside by adopting the theory and principles of Action Research which is a research methodology that can provide the course organizer emergent, responsive, action-oriented, participative and critically reflective insights for the immediate changes and amendments in order to improve the effect of teaching and learning experience. In the conclusion, how the learning and teaching experience of this trans-disciplinary design studio can offer us some observation that can help us reflect upon the constraints and division caused by the subject base curriculum will be pointed out. A series of concepts for course design and teaching strategies developed and implemented in this trans-disciplinary course are to be introduced as a way to promote learners’ self-motivated, collaborative, cross-disciplinary and student-centered learning skills. The outcome of this experimental course can exemplify an alternative approach that we could adopt in pursuing a remedy for dealing with the problematic issues of the current educational practice.

Keywords: course design, coaching strategy, subject base curriculum, trans-disciplinary

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Authors: Abiodun Oluwaseun Ibude

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Every now and then we hear of companies closing down their operations due to unethical practices like an overstatement of company’s balance sheet, concealing company’s debt, embezzlement of company’s fund, declaring false profit and so on. This has led to the liquidation of companies and the loss of investments of shareholders as well as the interest of other stakeholders. As a result of these ugly trends, there is need to put in place a formidable mechanism that will ensure that business activities are conducted in a healthy manner. It should also promote good ethics as well as ensure that the interest of stakeholders and the objectives of any organization is achieved within the confines of the law; wherein law exists to provide criminal penalties for falsification of documents and for conducting other irregularities. Based on the foregoing, it becomes imperative to ensure that steps are taken to stop this menace and face the challenges ahead. This calls for the practice of good governance. The purpose of this study is to identify various components of corporate governance and determine the impact of it on the performance of established organizations. A survey method with the use of questionnaire was applied in collecting data useful for this study which were later analyzed using correlation co-efficiency statistical tools in generating finding, making a conclusion, and necessary recommendation. From the research conducted, it was discovered that there are systems within organizations apart from regulatory agencies that ensure effective control of activities, promote accountability, and operational efficiency. However, some members of organizations fail to explore the usage of corporate governance and impact negatively of an organization’s performance. In conclusion, good corporate governance will not be achieved unless there is openness, honesty, transparency, accountability, and fairness.

Keywords: corporate governance, formidable mechanism, company’s balance sheet, stakeholders

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Authors: Martabolette Stecher

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Introductory: How is knowledge and ability to act on employable opportunities constructed among students and graduates at higher educations? This question have been drawn much attention by researchers, governments and universities in Denmark, since there has been an increases in the rate of unemployment among graduates from higher education. The fact that more than ten thousand graduates from higher education without the opportunity to get a job in these years has a tremendous impact upon the social economy in Denmark. Every time a student graduate from higher education and become unemployed, it is possible to trace upon the person´s chances to get a job many years ahead. This means that the tremendous rate of graduate unemployment implies a decrease in employment and lost prosperity in Denmark within a billion Danish Kroner scale. Basic methodologies: The present study investigates the construction of knowledge and ability to act upon employable opportunities among students and graduates at higher educations in Denmark in a literature review as well as a preliminary study of students from Aarhus University. 15 students from the candidate of drama have been engaging in an introductory program at the beginning of their candidate study, which included three workshops focusing upon the more personal matters of their studies and life. They have reflected upon this process during the intervention and afterwards in a semi-structured interview. Concurrently a thorough literature review has delivered key concepts for the exploration of the research question. Major findings of the study: It is difficult to find one definition of what employability encompasses, hence the overall picture of how to incorporate the concept is difficult. The present theory of employability has been focusing upon the competencies, which students and graduates are going to develop in order to become employable. In recent years there has been an emphasis upon the mechanism which supports graduates to trust themselves and to develop their self-efficacy in terms of getting a sustainable job. However, there has been little or no focus in the literature upon the idea of how students and graduates from higher education construct knowledge about and ability to act upon employable opportunities involving network of actors both material and immaterial network and meaningful relations for students and graduates in developing their enterprising behavior to achieve employment. The Act-network-theory combined with theory of entrepreneurship education suggests an alternative strategy to focus upon when explaining sustainable ways of creating employability among graduates. The preliminary study also supports this theory suggesting that it is difficult to emphasize a single or several factors of importance rather highlighting the effect of a multitude network. Concluding statement: This study is the first step of a ph.d.-study investigating this problem in Denmark and the USA in the period 2015 – 2019.

Keywords: employablity, graduates, action, opportunities

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Authors: Nirman Kumar Ojha

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Bamboo plantation can be integrated for natural embankment against flood and live fencing against wild animals, at the same time provide economic opportunity for the poor farmers as a sustainable solution and adaptation alternative. 2010 flood in the Rui River completely inundated fields of four VDCs in Madi, Chitwan National Park with extensive bank erosion. The main aim of this action research was to identify an economically sustainable natural embankment against flood and also providing wildlife friendly fencing to reduce human-wildlife conflict. Community people especially poor farmers were trained for soil testing, land identification, plantation, and the harvesting regime, nursery set up and intercropping along with bamboo plantation on the edge of the river bank in order to reduce or minimize soil erosion. Results show that farmers are able to establish cost efficient and economically sustainable river embankment with bamboo plantation also creating a fence for wildlife which has also promoted bamboo cultivation and conservation. This action research has amalgamated flood control and wildlife control with the livelihood of the farmers which otherwise would cost huge resource. Another major impact of the bamboo plantation is its role in climate change and its adaptation process reducing degradation and improving vegetation cover contributing to landscape management. Based on this study, we conclude that bamboo plantation in Madi, Chitwan promoted the livelihood of the poor farmers providing a sustainable economic solution to reduce bank erosion, human-wildlife conflict and contributes to landscape management.

Keywords: climate change and conservation, economic opportunity, flood control, national park

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Authors: R. Prinsloo

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis, and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: best interest of the child, children's rights, parent and child relationship, parental responsibilities and rights

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Authors: Wasantha Pushpakumara Hitihami Mudiyanselage

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Since recent past, Sri Lanka is highly vulnerable to reoccurring climate shocks that severely impact the food security, loss of human & animal lives, destructions of human settlements, displacement of people and damaging properties. Hence, the Government of Sri Lanka has taken important steps towards strengthening legal and institutional arrangements for Disaster Risks management in the country in May 2005. Puttalam administrative district is one of the disaster prone districts in Sri Lanka which constantly face the devastating consequences of the increasing natural disasters annually. Therefore disaster risk management will be a timely intervention in the area to minimize the adverse impacts of the disasters. The few functioning Disaster Risk management networks do not take children’s specific needs and vulnerabilities during emergencies into account. The most affected children and their families were evacuated to the government schools and temples and it was observed that children were left to roaming around as their parents were busy queuing up for relief goods and other priorities. In this sense, VOICE understands that the community has vital role that has to be played in facing challenges of disaster management in the area. During and after the disaster, it was viewed that some children were having psychological disorders which could be impacted negatively to children well–being. Need of child friendly space at emergency is a must action in the area to turn away negative impact coming from the hazards. VOICE with the support of national & international communities have established safer places for the children (Child Centered Spaces – CCS) and their families at emergencies. Village religious venues and schools were selected and equipped with necessary materials to be used for the children at emergency. Materials such as tools, stationeries, play materials, which couldn’t be easily found in surrounding environment, were provided for CCS centers. Village animators, youth and elders were given comprehensive training on Disaster management and their role at CCS. They did the facilitation in keeping children without fear and stress at flooding occurred in 2015 as well as they were able to improve their skills when working with children. Flooding in 2016, the government agencies have taken service of these village animators at early stage of flooding to make all disaster-related recovery actions productively & efficiently. This mechanism is sustained at village level that can be used for disaster events.

Keywords: child centered space, impacts, psychological disorders, village animators

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Authors: Sohail Ahmed, Ke Xing

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This research theoretically explored the evolution mechanism of enterprise technological innovation capability system (ETICS) from the perspective of complex adaptive systems (CAS). This research proposed an analytical framework for ETICS, its concepts, and theory by integrating CAS methodology into the management of the technological innovation capability of enterprises and discusses how to use the principles of complexity to analyze the composition, evolution, and realization of the technological innovation capabilities in complex dynamic environments. This paper introduces the concept and interaction of multi-agent, the theoretical background of CAS, and summarizes the sources of technological innovation, the elements of each subject, and the main clusters of adaptive interactions and innovation activities. The concept of multi-agents is applied through the linkages of enterprises, research institutions, and government agencies with the leading enterprises in industrial settings. The study was exploratory and based on CAS theory. Theoretical model is built by considering technological and innovation literature from foundational to state of the art projects of technological enterprises. On this basis, the theoretical model is developed to measure the evolution mechanism of the enterprise's technological innovation capability system. This paper concludes that the main characteristics for evolution in technological systems are based on the enterprise’s research and development personnel, investments in technological processes, and innovation resources are responsible for the evolution of enterprise technological innovation performance. The research specifically enriched the application process of technological innovation in institutional networks related to enterprises.

Keywords: complex adaptive system, echo model, enterprise technological innovation capability system, research institutions, multi-agents

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Authors: Nadine khadraoui, Rym Essid, Olfa Tabbene, Imen Chniba, Safa Boujemaa, Selim Jallouli, Nadia Fares, Behija Mlik, Boutheina Ben Abdelmoumen Mardassi

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Background and aim: Mycoplasma hominis is an opportunistic pathogen that can cause various gynecological infections such cervicitis, infertility, and, less frequently, extra-genital infections. Previous studies on the antimicrobial susceptibility of Mycoplasma hominis Tunisian strains have highlighted a significant resistance, even multi-resistance, to the most used antibiotic in the therapy of consequential infections. To address this concern, the present study aimed for the alternative of phytotherapy. Peganum harmala seed extract was tested as an antibacterial agent against multidrug-resistant M.hominis clinical strains. Material and Methods: Peganum harmala plant was collected from Ain Sebaa, Tabarka, North West region of Tunisia in April 2018, air-dried, grounded and extracted by different solvents.The crude methanolic extract was further partitioned with n-HEX, DCM, EtOAC and n-BuOl. Antibacterial activity was evaluated against M. hominis ATCC 23114 and 20 M. hominis clinical strains.The antimycoplasmal activity was tested by the microdilution method, and MIC values were determined. Phytochemical analysis and hemolytic activity on human erythrocytes were also performed. The active fraction was then subjected to purification, and the chemical identification of the active compound was investigated. Results: Among the tested fractions, the n-BuOH extract was the most active fraction since it exhibited an inhibitory effect against M. hominis ATCC 23114 and 80% of the tested clinical strains with MIC between 125 and 1000 µg/ml. The phytochemical analysis of the n-BuOH revealed its metabolic abundance in polyphenols, flavonoids and condensed tannin with levels of 257.37 mg AGE/g, 172.27 mg EC/g and 58.27 mg EC/g, respectively. In addition, P. harmala n-BuOH extract exhibited potent bactericidal activity against all M. hominis isolates with CMB values ranging between 125 and 4000 µg/ml. Further, the active fraction exhibited weak cytotoxicity effect at active concentrations when tested on human erythrocytes. The active compound was identified by gas chromatography–mass spectrometry as an indole alkaloid harmaline. Conclusion: In summary, Peganum harmala extract demonstrated an interesting anti-mycoplasmal activity against M. hominis Tunisian strains. Therefore, it could be considered as a potential candidate for the treatment of consequential infections. However, further studies are necessary to evaluate its mechanism of action in mycoplasmas.

Keywords: mycoplasma hominis, peganum harmala, antibioresistance, phytotherapy, phytochemical analysis

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Authors: Han Song, Tingting Wei, Dong Chen

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The combination of capital and rural areas in China has shown its great significance in promoting urban-rural integration and new-style urbanization, enhancing regional capacity for sustainable rural development and optimizing human settlement environment. The purpose of this study is to find capital operation mechanism in rural area and rural planning guidance in China. Based on case studies in Chinese rural areas, two types of capital operation mechanism in rural areas are summed up: intervention in the field of agriculture promoting the upgrading and innovation of agricultural industry chain, intervention in rural life and leisure areas updating rural connotation and form. In the light of experiences in Japan and Taiwan, it is proposed that government's norms and guidance, rural investment intensity and rural self-organization are three important factors for capital to drive rural development. It is also found that the unique land tenure and rural governance tradition are two important factors effecting the combination of capital and rural regions in China, which requires full attention in rational policy-making and rural planning. It comes to a conclusion as four directions of the overall reform of the rural planning: targeting at enhancing the viability of rural and sustainable capacity, encouraging differences in investment incentives and planning policies, providing land usage in the rural areas with planning support and reforming the village system. Directional guidance is also made for different types of capital investments, suggesting that capital should be rooted in agriculture and rural land to benefit farmers and update human settlements.

Keywords: capital, rural areas, rural planning, rural governance

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Authors: Valentina Narvaez Gaitan, Paula K. Rodriguez Ramirez, Derian D. Espinosa

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Corrective orthosis has great importance in orthopedic treatments providing assistance in improving mobility and stability in order to improve the quality of life for a different patient. The corrective orthosis studied in this article can correct deformities, reduce pain, and improve the ability to perform daily activities. This work describes the design and evaluation of a corrective orthosis for knee hyperextension. This orthosis is capable of generating a progressive and variable alignment of the joint, limiting the range of motion according to medical criteria. The main objective was to design a corrective knee orthosis capable of correcting knee hyperextension progressively to return to its natural angle with greater economic affordability and adjustable size. The limiting mechanism is based on a goniometer to determine the desired angles. The orthosis was made of acrylic to reduce costs and maintenance; neoprene is also used to make comfortable contact; additionally, Velcro was used in order to adjust the orthosis for various sizes. Simulations of static and fatigue analysis of the mechanism were performed to verify its resistance and durability under normal conditions. A biomechanical gait study of gait was carried out on 10 healthy subjects without the orthosis and limiting their knee extension capacity in a normal gait cycle with the orthosis to observe the efficiency of the proposed system. In the results obtained, the knee angle curves show that the maximum extension angle was the established angle by the orthosis. Showing the efficiency of the proposed design for different leg sizes.

Keywords: biomechanical study, corrective orthosis, efficiency, goniometer, knee hyperextension.

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Authors: Andy Alubaidy

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In this work, a robotic additive manufacturing system (RAMS) that is capable of three-dimensional (3D) printing in six degrees of freedom (DOF) with very high accuracy and virtually on any surface has been designed and built. One of the major shortcomings in existing 3D printer technology is the limitation to three DOF, which results in prolonged fabrication time. Depending on the techniques used, it usually takes at least two hours to print small objects and several hours for larger objects. Another drawback is the size of the printed objects, which is constrained by the physical dimensions of most low-cost 3D printers, which are typically small. In such cases, large objects are produced by dividing them into smaller components that fit the printer’s workable area. They are then glued, bonded or otherwise attached to create the required object. Another shortcoming is material constraints and the need to fabricate a single part using different materials. With the flexibility of a six-DOF robot, the RAMS has been designed to overcome these problems. A feeding mechanism using an adaptive Proportional-Integral-Derivative (PID) controller is utilized along with a national instrument compactRIO (NI cRIO), an ABB robot, and off-the-shelf sensors. The RAMS have the ability to 3D print virtually anywhere in six degrees of freedom with very high accuracy. It is equipped with an ABB IRB 120 robot to achieve this level of accuracy. In order to convert computer-aided design (CAD) files to digital format that is acceptable to the robot, Hypertherm Robotic Software Inc.’s state-of-the-art slicing software called “ADDMAN” is used. ADDMAN is capable of converting any CAD file into RAPID code (the programing language for ABB robots). The robot uses the generated code to perform the 3D printing. To control the entire process, National Instrument (NI) compactRIO (cRio 9074), is connected and communicated with the robot and a feeding mechanism that is designed and fabricated. The feeding mechanism consists of two major parts, cold-end and hot-end. The cold-end consists of what is conventionally known as an extruder. Typically, a stepper-motor is used to control the push on the material, however, for optimum control, a DC motor is used instead. The hot-end consists of a melt-zone, nozzle, and heat-brake. The melt zone ensures a thorough melting effect and consistent output from the nozzle. Nozzles are made of brass for thermo-conductivity while the melt-zone is comprised of a heating block and a ceramic heating cartridge to transfer heat to the block. The heat-brake ensures that there is no heat creep-up effect as this would swell the material and prevent consistent extrusion. A control system embedded in the cRio is developed using NI Labview which utilizes adaptive PID to govern the heating cartridge in conjunction with a thermistor. The thermistor sends temperature feedback to the cRio, which will issue heat increase or decrease based on the system output. Since different materials have different melting points, our system will allow us to adjust the temperature and vary the material.

Keywords: robotic, additive manufacturing, PID controller, cRIO, 3D printing

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Authors: Prince Kumar, Shamseer Kulangara Kandi, Diwan S. Rawat, Kasturi Mukhopadhyay

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Staphylococcus aureus is the most pathogenic of all staphylococci, a major cause of nosocomial infections, and known for acquiring resistance towards various commonly used antibiotics. Due to the widespread use of synthetic drugs, clinicians are now facing a serious threat in healthcare. The increasing resistance in staphylococci has created a need for alternatives to these synthetic drugs. One of the alternatives is a natural plant-based medicine for both disease prevention as well as the treatment of chronic diseases. Among such natural compounds, curcumin is one of the most studied molecules and has been an integral part of traditional medicines and Ayurveda from ancient times. It is a natural polyphenolic compound with diverse pharmacological effects, including anti-inflammatory, antioxidant, anti-cancerous and antibacterial activities. In spite of its efficacy and potential, curcumin has not been approved as a therapeutic agent yet, because of its low solubility, low bioavailability, and rapid metabolism in vivo. The presence of central β-diketone moiety in curcumin is responsible for its rapid metabolism. To overcome this, in the present study, curcuminoids were designed by modifying the central β-diketone moiety of curcumin into mono carbonyl moiety and their antibacterial potency against S. aureus ATCC 29213 was determined. Further, the mode of action and hemolytic activity of the most potent curcuminoids were studied. Minimum inhibitory concentration (MIC) and in vitro killing kinetics were used to study the antibacterial activity of the designed curcuminoids. For hemolytic assay, mouse Red blood cells were incubated with curcuminoids and hemoglobin release was measured spectrophotometrically. The mode of action of curcuminoids was analysed by membrane depolarization assay using membrane potential sensitive dye 3,3’-dipropylthiacarbocyanine iodide (DiSC3(5)) through spectrofluorimetry and membrane permeabilization assay using calcein-AM through flow cytometry. Antibacterial screening of the designed library (61 curcuminoids) revealed excellent in vitro potency of six compounds against S. aureus (MIC 8 to 32 µg/ml). Moreover, these six compounds were found to be non-hemolytic up to 225 µg/ml that is much higher than their corresponding MIC values. The in vitro killing kinetics data showed five of these lead compounds to be bactericidal causing >3 log reduction in the viable cell count within 4 hrs at 5 × MIC while the sixth compound was found to be bacteriostatic. Depolarization assay revealed that all the six curcuminoids caused depolarization in their corresponding MIC range. Further, the membrane permeabilization assay showed that all the six curcuminoids caused permeabilization at 5 × MIC in 2 hrs. This membrane depolarization and permeabilization caused by curcuminoids found to be in correlation with their corresponding killing efficacy. Both these assays point out that membrane perturbations might be a primary mode of action for these curcuminoids. Overall, the present study leads us six water soluble, non-hemolytic, membrane-active curcuminoids and provided an impetus for further research on therapeutic use of these lead curcuminoids against S. aureus.

Keywords: antibacterial, curcumin, minimum inhibitory concentration , Staphylococcus aureus

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