Search results for: online advertising mechanism

Authors: J. Bartnicka, J. A. Piedrabuena, R. Portilla, L. Moyano - Cuevas, J. B. Pagador, P. Augat, J. Tokarczyk, F. M. Sánchez Margallo

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Orthopaedic surgeries are characterized by a high degree of complexity. This is reflected by four main groups of resources: 1) surgical team which is consisted of people with different competencies, educational backgrounds and positions; 2) information and knowledge about medical and technical aspects of surgery; 3) medical equipment including surgical tools and materials; 4) space infrastructure which is important from an operating room layout point of view. These all components must be integrated and build a homogeneous organism for achieving an efficient and ergonomically correct surgical workflow. Taking this as a background, there was formulated a concept of international project, called “Online Vocational Training course on ergonomics for orthopaedic Minimally Invasive” (Train4OrthoMIS), which aim is to develop an e-learning tool available in 4 languages (English, Spanish, Polish and German). In the article, there is presented the first project research outcomes focused on three aspects: 1) ergonomic needs of surgeons who work in hospitals around different European countries, 2) the concept of structure of e-learning course, 3) the definition of tools and methods for knowledge assessment adjusted to users’ expectation. The methodology was based on the expert panels and two types of surveys: 1) on training needs, 2) on evaluation and self-assessment preferences. The major findings of the study allowed describing the subjects of four training modules and learning sessions. According to peoples’ opinion there were defined most expected test methods which are single choice test and right after quizzes: “True or False” and “Link elements”. The first project outcomes confirmed the necessity of creating a universal training tool for orthopaedic surgeons regardless of the country in which they work. Because of limited time that surgeons have, the e-learning course should be strictly adjusted to their expectation in order to be useful.

Keywords: international e-learning, ergonomics, orthopaedic surgery, Train4OrthoMIS

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Authors: Chamtouri I., Kechida M.

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Background: Evaluation has a prominent role in medical education and graduation. This evaluation has usually done in face-to-face, by written or oral questions. Simulation is increasingly taking a part as a method of evaluation. Due to the Covid-19 pandemic, which disrupted face-to-face evaluation, simulation using serious games (SG) is emerging in the field of training and assessment of medical students. The aim of our study is to compare the results of the evaluation of medical students by virtual simulation by online serious games versus clinical case-multiple choice questions (MCQ) and to assess the degree of satisfaction from these two evaluation methods. Methods: Medical students from the same study level were voluntarily participated in this study. Groupe 1 had an evaluation by SG dealing with “diagnosis and management of ST-segment elevationmyocardialinfarction (STEMI)alreadyprepared on the website www.Mediactiv.com. Groupe 2 were evaluated by clinical case-MCQ having thes same topic as SG. Results of the two groups were compared. Satisfaction questionnaire was filled by the two groups. Satisfaction degree was compared between the two groups. Results. In this study, 64 medical students (G1:31 and G2: 33) were enrolled. Obtaining complete notes in the "questioning" and "clinical examination" parts is significantly more important in-group 1 compared to group 2. No significant difference detected between the two groups in terms of “ECG interpretation” and “diagnosis of STEMI” parts. A greater number of students of group 1 obtained the full note compared to group 2 in “the initial treatment part” (54.8% vs. 39.4%; p = 0.04). Thirty learners (96.8%) in-group 1 obtained a total score ≥ 50% versus 69.7% in-group 2 (p = 0.004). The full score of 100% was obtained in three learners in-group1, while no student scored 100% in-group2 (p = 0.027). Medical evaluation using SG was reported as more innovative, fun, and realistic compared to evaluation by clinical case-MCQ. No significant difference detected between the two methods in terms of stress. Conclusion: Simulation by SG can be considered as an innovative and effective method in evaluating medical students with a higher degree of satisfaction.

Keywords: evaluation, serious games, medical students, satisfaction

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Authors: Maja Ruzic-Baf, Vedrana Keteles, Andrea Debeljuh

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Younger and younger children are now using a smartphone, a device which has become ‘a must have’ and the life of children would be almost ‘unthinkable’ without one. Devices are becoming lighter and lighter but offering an array of options and applications as well as the unavoidable access to the Internet, without which it would be almost unusable. Numerous features such as taking of photographs, listening to music, information search on the Internet, access to social networks, usage of some of the chatting and messaging services, are only some of the numerous features offered by ‘smart’ devices. They have replaced the alarm clock, home phone, camera, tablet and other devices. Their use and possession have become a part of the everyday image of young people. Apart from the positive aspects, the use of smartphones has also some downsides. For instance, free time was usually spent in nature, playing, doing sports or other activities enabling children an adequate psychophysiological growth and development. The greater usage of smartphones during classes to check statuses on social networks, message your friends, play online games, are just some of the possible negative aspects of their application. Considering that the age of the population using smartphones is decreasing and that smartphones are no longer ‘foreign’ to children of pre-school age (smartphones are used at home or in coffee shops or shopping centers while waiting for their parents, playing video games often inappropriate to their age), particular attention must be paid to a very sensitive group, the teenagers who almost never separate from their ‘pets’. This paper is divided into two sections, theoretical and empirical ones. The theoretical section gives an overview of the pros and cons of the usage of smartphones, while the empirical section presents the results of a research conducted in three elementary schools regarding the usage of smartphones and, specifically, their usage during classes, during breaks and to search information on the Internet, check status updates and 'likes’ on the Facebook social network.

Keywords: education, smartphone, social networks, teenagers

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Authors: Patience Oluchi Silas, Yemi Adeshina

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Financial transactions involving the use of the internet has become an important practice among commercial banks in Nigeria with the introduction of internet banking and this has improved banking efficiency in rending services to customers. However, customers in Lagos State are enslaved in the fear of insecurity, technical failure, inadequate operational facilities, including improper telecommunications and poor power supply. It is in line with this that this paper explores the obstacles faced by Lagosians, tourists, small scale business owners, companies, customers and the government's attitude in addressing the challenges associated with online banking system in Nigeria through relevant legislations. Internet banking has the potential to transform economic activity and achieve developmental goals. If the associated Challenges are addressed quickly, then it will have the desired impact on the Nigerian economy. In this study, Respondents, mostly bank employees and customers were issued well designed and structured questionnaires to effectively examine the new developments brought about by the introduction of Internet banking and the challenges inhibiting its adoption. Hypotheses were formulated to test assumptions and claims generated from the study. The results were statistically analyzed to address the issues of errors and chances, and at the end, the result of the statistical analysis shows that all especially insecurity, inadequate operational facilities and poor power supply are the significant factors affecting the adoption of internet banking services in Nigeria. The study recommends that for internet banking to assume a developmental dimension in Nigeria and for the country to be fully integrated and respected in global financial environment, the prevalent level of frauds in Lagos State and among Nigerians must first be addressed and the relevant local laws should be put in place and in consonance with international laws and conventions; get the citizens well educated on the intricacies of Internet usage and frauds.

Keywords: internet-banking, adoption, challenges, insecurity, legislation, fraud, Lagos state, statistics

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Authors: J. Izan, E.I. Tengku Azmina, F. Pey Thing

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Sustainability has been introduced globally since the emerging of the advancement of technology and product development in various aspects. This concept is regarded highly, listed among the seventeenth elements in Sustainable Development Goals (SDG), especially by developed countries in any of their development plans and being considered in the development of the developing countries. It is such as the concept of sustainability can undeniably provide a medium where the cost used by energy consumption and pollution problems can be greatly reduced. In Malaysia, many rules and policies had been advocated to achieve sustainability; however, the practice and implementation as well the enforcement to ensure its implementation are still not great. University, as an educational institution, shall practice and implement sustainability concepts in as much aspect as possible as a positive example for a wider community. University Malaysia Terengganu (UMT) has already published a blueprint guide in 2015, aims to introduce and implement sustainable practice in the university, and solid waste is one of the key elements highlighted. This study was conducted to determine the status of solid waste management practice among the university community associated with several factors that facilitate the room for sustainable management, as drawn in the established blueprint document. The quantitative analysis was carried out via survey conducted online, acquired the questions on green campus concept and implementation in general and solid waste in particular. The results showed that community UMT showed a high level of awareness and knowledge on sustainable solid waste; however, low percentage in managing solid waste in a sustainable manner. Respondents suggested that stringent guidelines and the establishment of policy greatly help in the realization and enforcement of sustainable solid waste handling and management. Facilities such as waste collection centre with separation and segregation containers will motivate the community to practice 3Rs on a daily basis. This will eventually reduce the generation of waste need to be sent to landfill hence reduce the disposal cost. Prolong, and continuous campaign on sustainable solid waste management need to be carried out more frequently.

Keywords: management, solid waste, sustainability, university

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Authors: Yasir Arafat, Asma Shah, Hua Shao

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Background and Aims: Legume/cereal intercropping is used worldwide for enhancement in biomass and yield of cereal crops. However, because of intercropping, the belowground biological and chemical interactions and their effect on physiological parameters and yield of crops are limited. Methods: Wheat faba bean (WF) intercropping was designed to understand the underlying changes in the soil's chemical environment, soil microbial communities, and effect on growth and yield parameters. Experimental plots were established as having no root partition (NRP), semi-root partition (SRP), complete root partition (CRP), and their sole cropping (CK). Low molecular weight organic acids (LMWOAs) were determined by GC-MS, and high throughput sequencing of the 16S rRNA gene was carried out to screen microbial structure and composition in different root partitions of the WF intercropping system. Results: We show that intercropping induced a shift in the relative abundance of some genera of plant growth promoting rhizobacteria (PGPR) such as Allorhizobium, Neorhizobium, Pararhizobium, and Rhizobium species and resulted in better growth and yield performance of wheat. Moreover, as the plant's distance of wheat from faba beans decreased, the diversity of microbes increased, and a positive effect was observed on physiological traits and crop yield. Furthermore, an abundance and positive correlations of palmitic acid, arachidic acid, stearic acid, and 9-Octadecenoic with PGPR were recorded in the root zone of WF intercropping, which can play an important role in this facilitative mechanism of enhancing growth and yield of cereals. Conclusion: The two treatments clearly affected soil microbial and chemical composition, which can be reflected in growth and yield enhancement.

Keywords: intercropping, microbial community, LMWOAs, PGPR, soil chemical environment

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Authors: Shamim Ahsan

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Abstract Global digital advances associated with consumer’s strong inclination for the state of art digital technologies is causing overwhelming social and environmental challenges for global community. During recent years not only economic advances of electronic industries has taken place at steadfast rate, also the generation of e-waste outshined the growth of any other types of wastes. The estimated global e-waste volume is expected to reach 65.4 million tons annually by 2017. Formal recycling practices in developed countries are stemming economic liability, opening paths for illegal trafficking to developing countries. Informal crude management of large volume of e-waste is transforming into an emergent environmental and health challenge in. Contrariwise, in several studies formal and informal recycling of e-waste has also exhibited potentials for economic returns both in developed and developing countries. Some research on China illustrated that from large volume of e-wastes generation there are recycling potential in evolving from ∼16 (10−22) billion US$ in 2010, to an anticipated ∼73.4 (44.5−103.4) billion US$ by 2030. While in another study, researcher found from an economic analysis of 14 common categories of waste electric and electronic equipment (WEEE) the overall worth is calculated as €2.15 billion to European markets, with a potential rise to €3.67 billion as volumes increase. These economic returns and environmental protection approaches are feasible only when sustainable policy options are embraced with stricter regulatory mechanism. This study will critically review current researches to stipulate how global e-waste generation and sustainable e-waste recycling practices demonstrate future economic development potential in terms of both quantity and processing capacity, also triggering complex some environmental challenges.

Keywords: E-Waste, , Generation, , Economic Potential, Recycling

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Authors: Szu-Chieh Yu, Pei-Chin Chiand, Chih-Yi Lin, Yi-Wen Chien

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UV radiation from sunlight cause numbers of acute and chronic skin damage which can result in inflammation, immune changes, physical changes and DNA damage that facilitates skin aging and the development of skin carcinogenesis. Reactive oxygen species (ROS) are generated by excessive solar UV radiation, resulting in oxidative damage to cellar components, proteins, lipids, and nucleic acids. Thus, antioxidation plays an important role that protects skin against ROS-induced injury. Safflower (Carthamus tinctorius L.) is an important Chinese medicine contained abundance flavones and hydroxysafflor yellow A (HSYA) which is main active ingredient. HSYA is part of quinochalcone and has unique structures of hydroxy groups that provided the antioxidant effect. In this study, the aim was to investigate the protective role of HYSA in human keratinocytes (HaCaT) against UVA-induced oxidative damage and the possible mechanism. The HaCaT cells were UVA-irradiated and the effects of HYSA on cell viability, reactive oxygen species generation, DNA fragmentation and lipid peroxidation were measured. The mRNA expression of matrix metalloproteinase Ι (MMP Ι), cyclooxygenase-2 (COX-2) were determined by RT-PCR. In this study, UVA exposure lead to decrease in cell viability and increase in reactive oxygen species generation in HaCaT cells. HYSA could effectively increase the viability of HaCaT cells after UVA exposure and protect them from UVA-induced oxidative stress. Moreover, HYSA can reduce inflammation through inhibition the mRNA expression of MMP Ι and COX-2. Our results suggest that HSYA can act as a free radical scavenger while keratinocytes were photodamaged. HYSA could be a useful natural medicine for the protection of epidermal cells from UVA-induced damage and will be developed into products for skin care.

Keywords: HaCaT keratinocytes, hydroxysafflor yellow A (HSYA), MMP Ι, oxidative stress

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Authors: Preet Gill, Danus Ravindran

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These The COVID-19 pandemic resulted in widespread implications for medical specialist training programs worldwide, including radiology. The objective of this study was to investigate the impact of COVID-19 on the Australian and New Zealand radiology trainee experience and well-being, as well as to compare the Australasian experience with that reported by other countries. An anonymised electronic online questionnaire was disseminated to all training members of the Royal Australian and New Zealand College of Radiologists who were radiology trainees during the 2020 – 2022 clinical years. Trainees were questioned about their experience from the beginning of the COVID-19 pandemic in Australasia (March 2020) to the time of survey completion. Participation was voluntary. Questions assessed the impact of the pandemic across multiple domains, including workload (inpatient/outpatient & individual modality volume), teaching, supervision, external learning opportunities, redeployment and trainee wellbeing. Survey responses were collated and compared with other peer reviewed publications. Answer options were primarily in categorical format (nominal and ordinal subtypes, as appropriate). An opportunity to provide free text answers to a minority of questions was provided. While our results mirror that of other countries, which demonstrated reduced case exposure and increased remote teaching and supervision, responses showed variation in the methods utilised by training sites during the height of the pandemic. A significant number of trainees were affected by examination cancellations/postponements and had subspecialty training rotations postponed. The majority of trainees felt that the pandemic had a negative effect on their training. In conclusion, the COVID-19 pandemic has had a significant impact on radiology trainees across Australia and New Zealand. The present study has highlighted the extent of these effects, with most aspects of training impacted. Opportunities exist to utilise this information to create robust workplace strategies to mitigate these negative effects should the need arise in the future.

Keywords: COVID-19, radiology, training, pandemic

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Authors: Samuel O. Akande

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The human-induced climate change is likely to have severe consequences on forest ecosystems in Nigeria. Recent discussions and emphasis on issues concerning the environment justify the need for this research which examined deforestation monitoring in Oban Forest, Nigeria using Remote Sensing techniques. The Landsat images from TM (1986), ETM+ (2001) and OLI (2015) sensors were obtained from Landsat online archive and processed using Erdas Imagine 2014 and ArcGIS 10.3 to obtain the land use/land cover and Normalized Differential Vegetative Index (NDVI) values. Ground control points of deforested areas were collected for validation. It was observed that the forest cover decreased in area by about 689.14 km² between 1986 and 2015. The NDVI was used to determine the vegetation health of the forest and its implications on agricultural sustainability. The result showed that the total percentage of the healthy forest cover has reduced to about 45.9% from 1986 to 2015. The results obtained from analysed questionnaires shown that there was a positive correlation between the causes and effects of deforestation in the study area. The coefficient of determination value was calculated as R² ≥ 0.7, to ascertain the level of anthropogenic activities, such as fuelwood harvesting, intensive farming, and logging, urbanization, and engineering construction activities, responsible for deforestation in the study area. Similarly, temperature and rainfall data were obtained from Nigerian Meteorological Agency (NIMET) for the period of 1986 to 2015 in the study area. It was observed that there was a significant increase in temperature while rainfall decreased over the study area. Responses from the administered questionnaires also showed that futile destruction of forest ecosystem in Oban forest could be reduced to its barest minimum if fuelwood harvesting is disallowed. Thus, the projected impacts of climate change on Nigeria’s forest ecosystems and environmental stability is better imagined than experienced.

Keywords: deforestation, ecosystems, normalized differential vegetative index, sustainability

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Authors: Johanrik, Arini Apriliani, Fikri Haikal, Dias Yuca, Muhammad Abdul Latif, Edijanti Goenarwo, Nurita Pratama Sari

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Diarrhea is one of the leading causes of morbidity and mortality in many countries, as well as responsible for the deaths of millions of people each year. Previous research showed that the leaves, bark, and root bark of kedondong contains saponins, tannins, and flavonoids. Tannins have anti-diarrheal effects that work as the freeze of protein/astringent, and may inhibit the secretion of chloride over the tannate bonding between protein in the intestines. Chemical compounds of flavonoids also have an effect as anti-diarrheal block receptors Cl ˉ in intestinal thus reducing the secretion of Cl ˉ to the intestinal lume .This research aims to know the anti-diarrheal activity of extracts kedondong leaf in mice Balb/C strain males in vivo. This research also proves kedondong leaves as an anti-diarrhea through trial efficacy of kedondong leaves as antisekretori and antimotilitas. This research using post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. If the data obtained homogenous then using ANOVA test. This research using ethanolic extracts kedondong leaf 200, 400 and 800 mg/kgBW to prove there is anti-diarrhea it makes into six treatment groups, for anti-secretory it makes into five treatment groups and anti-motility became five treatment groups. The result showed dose of ethanolic extracts kedondong leaf 800 mg/kgBW have significant value (p<0.005). The conclusion from this extracts kedondong leaf research 800 mg/kgBW have pharmacological effects as antidiarrhea on Balb/C strain male mice with a mechanism of action as anti-secretory and anti-motility.

Keywords: anti-diarrhea, anti-secretory, anti-motility, kedondong leaf

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Authors: Dina Tawfic, Robert Hassan

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The current chapter addresses Al-Azhar's strategy to counter extremism in tandem with reflecting on the ideology of the Islamic establishment itself. The topic is motivated by the fact that some of the Western governments have been relying on Al-Azhar to counter the ideology of Islamist radicalism and violent extremism, in particular during the rise of the Islamic State in Syria and Iraq (known as ISIS/ ISIL/ Daesh) in 2014/2015. In his visit to Egypt in June 2016, Brett McGurk, the then U.S. envoy for the global coalition to counter ISIS, commended Al-Azhar’s “intellectual and reforming role” in refuting the ideology of extremism. On the other hand, Egyptian liberal intellectuals, such as Farag Fouda (1945- 1992) and Nasr Hamed Abu Zeid (1943-2010), had always questioned the ideological capability of Al-Azhar to counter extremism, citing the rigidity and resistance of the Islamic establishment to carry out genuine reformation. This chapter aims to discuss the following research questions: what is the strategy of Al-Azhar to counter extremism? Does Al-Azhar have a solid strategy to combat online propaganda produced by violent extremist groups? Is it applicable to identify Al-Azhar ideological identity? and is it capable of countering extremism? To answer these questions, I conducted intensive interviews with seven senior scholars and officials at Al-Azhar and the Endowments ministry from September to December 2020. Using a qualitative approach as a backdrop, this project uses semi-structured interviews to collect data. Participants were briefed on the purpose of the study and consented to be interviewed and to record their interviews. Some of the participants chose to conceal their names. All the interviews were conducted in Arabic via Zoom. The researcher then transcribed and translated the interviews into English. A purposive sample is used to select the seven interviewees, based on their prominence and experience in the field of counter-extremism and Al-Azhar affairs. The researcher uses a snowball sample to select the sample, in which a personal contact recommends other officials within the establishment.

Keywords: Al-Azhar, Egypt, Counter-Extremism, Political Islam, Ideology

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Authors: Vishal Pareek, Shubham Gupta, Sushil Chandra Jain

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With increasing high-speed computation demand the power consumption, heat dissipation and chip size issues are posing challenges for logic design with conventional technologies. Recovery of bit loss and bit errors is other issues that require reversibility and fault tolerance in the computation. The reversible computing is emerging as an alternative to conventional technologies to overcome the above problems and helpful in a diverse area such as low-power design, nanotechnology, quantum computing. Bit loss issue can be solved through unique input-output mapping which require reversibility and bit error issue require the capability of fault tolerance in design. In order to incorporate reversibility a number of combinational reversible logic based circuits have been developed. However, very few sequential reversible circuits have been reported in the literature. To make the circuit fault tolerant, a number of fault model and test approaches have been proposed for reversible logic. In this paper, we have attempted to incorporate fault tolerance in sequential reversible building blocks such as D flip-flop, T flip-flop, JK flip-flop, R-S flip-flop, Master-Slave D flip-flop, and double edge triggered D flip-flop by making them parity preserving. The importance of this proposed work lies in the fact that it provides the design of reversible sequential circuits completely testable for any stuck-at fault and single bit fault. In our opinion our design of reversible building blocks is superior to existing designs in term of quantum cost, hardware complexity, constant input, garbage output, number of gates and design of online testable D flip-flop have been proposed for the first time. We hope our work can be extended for building complex reversible sequential circuits.

Keywords: parity preserving gate, quantum computing, fault tolerance, flip-flop, sequential reversible logic

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Authors: Binh T. T. Nguyen, Zhenyu Li, Eric Yap, Yi Zhang, Ai-Qun Liu

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Silicon-photonic-sensor system is an emerging class of analytical technologies that use evanescent field wave to sensitively measure the slight difference in the surrounding environment. The wavelength shift induced by local refractive index change is used as an indicator in the system. These devices can be served as sensors for a wide variety of chemical or biomolecular detection in clinical and environmental fields. In our study, a system including a silicon-based micro-ring resonator, microfluidic channel, and optical processing is designed, fabricated for biomolecule detection. The system is demonstrated to detect Clostridium botulinum type A neurotoxin (BoNT) in different water sources. BoNT is one of the most toxic substances known and relatively easily obtained from a cultured bacteria source. The toxin is extremely lethal with LD50 of about 0.1µg/70kg intravenously, 1µg/ 70 kg by inhalation, and 70µg/kg orally. These factors make botulinum neurotoxins primary candidates as bioterrorism or biothreat agents. It is required to have a sensing system which can detect BoNT in a short time, high sensitive and automatic. For BoNT detection, silicon-based micro-ring resonator is modified with a linker for the immobilization of the anti-botulinum capture antibody. The enzymatic reaction is employed to increase the signal hence gains sensitivity. As a result, a detection limit to 30 pg/mL is achieved by our silicon-photonic sensor within a short period of 80 min. The sensor also shows high specificity versus the other type of botulinum. In the future, by designing the multifunctional waveguide array with fully automatic control system, it is simple to simultaneously detect multi-biomaterials at a low concentration within a short period. The system has a great potential to apply for online, real-time and high sensitivity for the label-free bimolecular rapid detection.

Keywords: biotoxin, photonic, ring resonator, sensor

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Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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Authors: V. Karuppaiah, J. C. Padaria, C. Srivastava

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The tobacco caterpillar, Spodoptera litura Fab (Lepidoptera: Noctuidae) is a polyphagous pest various field and horticulture crops in India. Pest had virtually developed resistance to all commonly used insecticides. Enhanced detoxification is the prime mechanism that is dictated by detoxification different enzymes and carboxylesterase is one of the major enzyme responsible development of resistance. In India, insecticide resistance studies on S. litura are mainly deployed on detoxification enzymes activity and investigation at gene level alteration i.e. at nucleotide level is very merger. In the present study, we collected the S. litura larvae from three different cauliflower growing belt viz., IARI, New Delhi (Delhi), Palari, Sonepat (Haryana) and Varanasi (Uttar Pradesh) to study the role of carboxylesterase activity and its gene level variation The CarE activity was measured using UV-VIS spectrophotometer with 3rd instar larvae of S. litura. The elevated activity of CarE was observed in Sonepat strain (28.09 ± 0.09 µmol/min/mg of protein) followed by Delhi (26.72 ± 0.04 µmol/min/mg of protein) and Varanasi strain (10.00 ± 0.44 µmol/min/mg of protein) of S. litura. The genomic DNA was isolated from 3rd instar larvae and CarE gene was amplified using a primer sequence, F:5’tccagagttccttgtcaggcac3’; R:5’ctgcatcaagcatgtctc3. CarE gene, about 500bp was partially amplified, sequenced and submitted to NCBI (Accession No. KF835886, KF835887 and KF835888). The sequence data revealed polymorphism at nucleotide level in all the three strains and gene found to have 88 to 97% similarity with previous available nucleotide sequences of S. litura, S. littoralis and S. exiqua. The polymorphism at the nucleotide level could be a reason for differential activity of carboxylesterase enzymes among the strains. However, investigation at gene expression level would be useful to analyze the overproduction of carboxylesterase enzyme.

Keywords: carboxylesterase, CarE gene, nucleotide polymorphism, insecticide resistance, spodoptera litura

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Authors: Anna Rhodora A. Solar, Jan Emil N. Langomez

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Social Media plays a crucial role in influencing Philippine public opinion with regard to a variety of socio-political issues. This became evident in the massacre of 44 members of the Special Action Force (SAF 44) tasked by the Philippine government to capture one of the US Federal Bureau of Investigation’s most wanted terrorists. The incident was said to be perpetrated by members of the Moro Islamic Liberation Front and the Bangsamoro Islamic Freedom Fighters. Part of the online discourse within Philippine cyberspace sparked intense debates on Filipino Muslim identity, with several Facebook viral posts linking Islam as a factor to the tragic event. Facebook is considered to be the most popular social media platform in the Philippines. As such, this begs the question of the extent to which social media, specifically Facebook, shape the perceptions of Filipinos on Filipino Muslims. This study utilizes Habermas’ theory of communicative action as it offers an explanation on how public sphere such as social media could be a network for communicating information and points of view through free and open dialogue among equal citizens to come to an understanding or common perception. However, the paper argues that communicative action which is aimed at reaching understanding free from force, and strategic action which is aimed at convincing someone through argumentation may not necessarily be mutually exclusive since reaching an understanding can also be considered as a result of convincing someone through argumentation. Moreover, actors may clash one another in their ideas before reaching common understanding, hence the presence of force. Utilizing content analysis on the Facebook posts with Islamic component that went viral after the massacre of the SAF 44, this paper argues that framing the image of Filipino Muslims through Facebook reflects both communicative and strategic actions. Moreover, comment threads on viral posts manifest force albeit implicit.

Keywords: communication, Muslim, Philippines, social media

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Authors: Celeste Lawson

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Learning to embrace and value teamwork assessment at a university level is critical for students, as graduates enter a real-world working environment where teamwork is likely to occur virtually. Student disdain for teamwork exercises is an area often overlooked or disregarded by academics. This research explored the implementation of an online teamwork assessment approach at a regional Australian university with a significant cohort of Distance Education students. Students had disliked teamwork for three reasons: it was not relevant to their study, the grading was unfair amongst team members, and managing the task was challenging in a virtual environment. Teamwork assessment was modified so that the task was an authentic task that could occur in real-world practice; team selection was based on the task topic rather than randomly; grading was based on the individual’s contribution to the task, and students were provided virtual team management skills as part of a the assessment. In this way, management of the team became an output of the task itself. Data was gathered over three years from student satisfaction surveys, failure rates, attrition figures, and unsolicited student comments. In one unit where this approach was adopted (Advanced Public Relations), student satisfaction increased from 3.6 (out of 5) in 2012 to 4.6 in 2016, with positive comments made about the teamwork approach. The attrition rate for another unit (Public Relations and the Media) reduced from 20.7% in 2012 to 2.2% in 2015. In 2012, criticism of teamwork assessment made up 50% of negative student feedback in Public Relations and the Media. By 2015, following the successful implementation of the teamwork assessment approach, only 12.5% of negative comments on the student satisfaction survey were critical of teamwork, while 33% of positive comments related to a positive teamwork experience. In 2016, students explicitly nominated teamwork as the best part of this unit. The approach is transferable to other disciplines and was adopted by other academics within the institution with similar results.

Keywords: assessment, distance education, teamwork, virtual

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Authors: Mahzabin Afroz, Indubhushan Patnaikuni, Srikanth Venkatesan

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It is well-known that fly ash can be used in high volume as a partial replacement of cement to get beneficial effects on concrete. High volume fly ash (HVFA) concrete is currently emerging as a popular option to strengthen by fiber. Although studies have supported the use of fibers with fly ash, a unified model along with the incorporation into finite element software package to estimate the maximum flexural loads need to be developed. In this study, nonlinear finite element analysis of steel fiber reinforced high strength HVFA concrete beam under static loadings was conducted to investigate their failure modes in terms of ultimate load. First of all, the experimental investigation of mechanical properties of high strength HVFA concrete was done and validates with developed numerical model with the appropriate modeling of element size and mesh by ANSYS 16.2. To model the fiber within the concrete, three-dimensional random fiber distribution was simulated by spherical coordinate system. Three types of high strength HVFA concrete beams were analyzed reinforced with 0.5, 1 and 1.5% volume fractions of steel fibers with specific mechanical and physical properties. The result reveals that the use of nonlinear finite element analysis technique and three-dimensional random fiber orientation exhibited fairly good agreement with the experimental results of flexural strength, load deflection and crack propagation mechanism. By utilizing this improved model, it is possible to determine the flexural behavior of different types and proportions of steel fiber reinforced HVFA concrete beam under static load. So, this paper has the originality to predict the flexural properties of steel fiber reinforced high strength HVFA concrete by numerical simulations.

Keywords: finite element analysis, high volume fly ash, steel fibers, spherical coordinate system

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Authors: Radhwane Boudjelthia

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The most recent earthquakes occurred in the world have killed thousands of people and severe damage. For all the actors involved in the building process, the earthquake is the litmus test for construction. The goal we set ourselves is to contribute to the implementation of a thoughtful approach to the seismic protection of structures. For many engineers, the most conventional approach to protection works (buildings and bridges) the effects of earthquakes is to increase rigidity. This approach is not always effective, especially when there is a context that favors the phenomenon of resonance and amplification of seismic forces. Therefore, the field of earthquake engineering has made significant inroads, among others catalyzed by the development of computational techniques in computer form and the use of powerful test facilities. This has led to the emergence of several innovative technologies, such as the introduction of special devices insulation between infrastructure and superstructure. This approach, commonly known as "seismic isolation," to absorb the significant efforts without the structure is damaged and thus ensuring the protection of lives and property. In addition, the restraints to the construction by the ground shaking are located mainly at the supports. With these moves, the natural period of construction is increasing, and seismic loads are reduced. Thus, there is an attenuation of the seismic movement. Likewise, the insulation of the base mechanism may be used in combination with earthquake dampers in order to control the deformation of the insulation system and the absolute displacement of the superstructure located above the isolation interface. On the other hand, only can use these earthquake dampers to reduce the oscillation amplitudes and thus reduce seismic loads. The use of damping devices represents an effective solution for the rehabilitation of existing structures. Given all these acceleration reducing means considered passive, much research has been conducted for several years to develop an active control system of the response of buildings to earthquakes.

Keywords: earthquake, building, seismic forces, displacement, resonance, response.

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Authors: Andres Bautista, Alicia Porras, Juan P. Casas, Maribel Silva

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The Colombian aeronautical industry has stimulated research in the mechanical behavior of materials under different loading conditions aircrafts are generally exposed during its operation. The Calima T-90 is the first military aircraft built in the country, used for primary flight training of Colombian Air Force Pilots, therefore, it may be exposed to adverse operating situations such as hard landings which cause impact loads on the aircraft that might produce the impact fatigue phenomenon. The Calima T-90 structure is mainly manufactured by composites materials generating assemblies and subassemblies of different components of it. The main method of bonding these components is by using adhesive joints. Each type of adhesive bond must be studied on its own since its performance depends on the conditions of the manufacturing process and operating characteristics. This study aims to characterize the typical adhesive joints of the aircraft under usual loads. To this purpose, the evaluation of the effect of adhesive thickness on the mechanical performance of the joint under quasi-static loading conditions, constant amplitude fatigue and cyclic impact fatigue using single lap-joint specimens will be performed. Additionally, using a double cantilever beam specimen, the influence of the thickness of the adhesive on the crack growth rate for mode I delamination failure, as a function of the critical energy release rate will be determined. Finally, an analysis of the fracture surface of the test specimens considering the mechanical interaction between the substrate (composite) and the adhesive, provide insights into the magnitude of the damage, the type of failure mechanism that occurs and its correlation with the way crack propagates under the proposed loading conditions.

Keywords: adhesive, composites, crack propagation, fatigue

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Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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Authors: Laroussi Chaabane, Amel El Ghali, Emmanuel Beyou, Mohamed Hassen V. Baouab

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In this research, the functionalization of graphene oxide sheets by ethylenediamine (EDA) was accomplished and followed by the grafting of bis(2-pyridylmethyl) amino group (BPED) onto the activated graphene oxide sheets in the presence of chloroacetylchloride (CAC) and then combined with magnetic nanoparticles (Fe₃O₄NPs) to produce a magnetic graphene-based composite [(Go-EDA-CAC)@Fe₃O₄NPs-BPED]. The physicochemical properties of [(Go-EDA-CAC)@Fe₃O₄NPs-BPED] composites were investigated by Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA). Additionally, the catalysts can be easily recycled within ten seconds by using an external magnetic field. Moreover, [(Go-EDA-CAC)@Fe₃O₄NPs-BPED] was used for removing Cu(II) ions from aqueous solutions using a batch process. The effect of pH, contact time and temperature on the metal ions adsorption were investigated, however weakly dependent on ionic strength. The maximum adsorption capacity values of Cu(II) on the [(Go-EDA-CAC)@Fe₃O₄NPs-BPED] at the pH of 6 is 3.46 mmol.g⁻¹. To examine the underlying mechanism of the adsorption process, pseudo-first, pseudo-second-order, and intraparticle diffusion models were fitted to experimental kinetic data. Results showed that the pseudo-second-order equation was appropriate to describe the Cu (II) adsorption by [(Go-EDA-CAC)@Fe₃O₄NPs-BPED]. Adsorption data were further analyzed by the Langmuir, Freundlich, and Jossens adsorption approaches. Additionally, the adsorption properties of the [(Go-EDA-CAC)@Fe₃O₄NPs-BPED], their reusability (more than 6 cycles) and durability in the aqueous solutions open the path to removal of Cu(II) from water solution. Based on the results obtained, we report the activity of Cu(II) supported on [(Go-EDA-CAC)@Fe₃O₄NPs-BPED] as a catalyst for the cross-coupling of symmetric alkynes.

Keywords: graphene, magnetic nanoparticles, adsorption kinetics/isotherms, cross coupling

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Authors: Hao Yang, Lei Chen, Ting Mei, Jianbang Zheng

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Currently, the uncooled PbSe photodetectors in the mid-infrared range (2-5μm) with sensitization technology extract more photoelectric response than traditional ones, and enable the room temperature (300K) photo-detection with high detectivity, which have attracted wide attentions in many fields. This technology generally contains the film fabrication with vapor phase deposition (VPD) and a sensitizing process with doping of oxygen and iodine. Many works presented in the recent years almost provide and high temperature activation method with oxygen/iodine vapor diffusion, which reveals that oxygen or iodine plays an important role in the sensitization of PbSe material. In this paper, we provide our latest experimental results and discussions in the stoichiometry of oxygen and iodine and its influence on the polycrystalline structure and photo-response. The experimental results revealed that crystal orientation was transformed from (200) to (420) by sensitization, and the responsivity of 5.42 A/W was gained by the optimal stoichiometry of oxygen and iodine with molecular density of I2 of ~1.51×1012 mm-3 and oxygen pressure of ~1Mpa. We verified that I2 plays a role in transporting oxygen into the lattice of crystal, which is actually not its major role. It is revealed that samples sensitized with iodine transform atomic proportion of Pb from 34.5% to 25.0% compared with samples without iodine from XPS data, which result in the proportion of about 1:1 between Pb and Se atoms by sublimation of PbI2 during sensitization process, and Pb/Se atomic proportion is controlled by I/O atomic proportion in the polycrystalline grains, which is very an important factor for improving responsivity of uncooled PbSe photodetector. Moreover, a novel sensitization and dopant activation method is proposed using oxygen ion implantation with low ion energy of < 500eV and beam current of ~120μA/cm2. These results may be helpful to understanding the sensitization mechanism of polycrystalline lead salt materials.

Keywords: polycrystalline PbSe, sensitization, transport, stoichiometry

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Authors: Souhir Abid

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The growing interest in vegetal biomass as an alternative for fossil resources has stimulated the development of numerous classes of monomers. Polymers from renewable resources have attracted an increasing amount of attention over the last two decades, predominantly due to two major reasons (i) firstly environmental concerns, and (ii) secondly the use of monomers from renewable feedstock is a steadily growing field of interest in order to reduce the amount of petroleum consumed in the chemical industry and to open new high-value-added markets to agriculture. Furanic polymers have been considered as alternative environmentally friendly polymers. In our earlier work, modifying furanic polyesters by incorporation of amide functions along their backbone, lead to a particular class of polymer ‘poly(ester-amide)s’, was investigated to combine the excellent mechanical properties of polyamides and the biodegradability of polyesters. As a continuation of our studies on this family of polymer, a series of furanic poly(ester-amide)s bearing sulfonate groups in the main chain were synthesized from 5,5’-Isopropylidene-bis(ethyl 2-furoate), dimethyl 5-sodiosulfoisophthalate, ethylene glycol and hexamethylene diamine by melt polycondensation using zinc acetate as a catalyst. In view of the complexity of the NMR spectrum analysis of the resulting sulfonated poly(ester-amide)s, we found that it is useful to prepare initially the corresponding homopolymers: sulfonated polyesters and polyamides. Structural data of these polymers will be used as a basic element in 1H NMR characterization. The hydrolytic degradation in acidic aqueous conditions (pH = 4,35 ) at 37 °C over the period of four weeks show that the mechanism of the hydrolysis of poly(ester amide)s was elucidated in relation with the microstructure. The strong intermolecular hydrogen bonding interactions between amide functions and water molecules increases the hydrophilicity of the macromolecular chains and consequently their hydrolytic degradation.

Keywords: furan, hydrolytic degradation, polycondensation, poly(ester amide)

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Authors: Charles Sikwanda

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The use of geosynthetic materials in geotechnical engineering projects has rapidly increased over the past several years. These materials have resulted in improved performance and cost reduction of geotechnical structures as compared to the use of conventional materials. However, working with geosynthetics requires knowledge of interface parameters for design. These parameters are typically determined by the large direct shear device in accordance with ASTM-D5321 and ASTM-D6243 standards. Although these laboratory tests are standardized, the quality of the results can be largely affected by several factors that include; the shearing rate, applied normal stress, gripping mechanism, and type of the geosynthetic specimens tested. Amongst these factors, poor surface gripping of a specimen is the major source of the discrepancy. If the specimen is inadequately secured to the shearing blocks, it experiences progressive failure and shear strength that deviates from the true field performance of the tested material. This leads to inaccurate, unsafe, and cost ineffective designs of projects. Currently, the ASTM-D5321 and ASTM-D6243 standards do not provide a standardized gripping system for geosynthetic shear strength testing. Over the years, researchers have come up with different gripping systems that can be used such as; glue, metal textured surface, sandblasting, and sandpaper. However, these gripping systems are regularly not adequate to sufficiently secure the tested specimens to the shearing device. This has led to large variability in test results and difficulties in results interpretation. Therefore, this study was aimed at determining the effects of gripping systems in geosynthetic interface shear strength testing using a 300 x 300 mm direct shear box. The results of the research will contribute to easy data interpretation and increase result accuracy and reproducibility.

Keywords: geosynthetics, shear strength parameters, gripping systems, gripping

Procedia PDF Downloads 175

Authors: Umer Masood Chaudry, Hafiz Muhammad Rehan Tariq, Chung-soo Kim, Tea-sung Jun

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This study explored the influence of pre-stretching temperature on the microstructural characteristics and deformation behavior of AZ61 magnesium alloy and its implications on grain growth during subsequent annealing. AZ61 alloy was stretched to 5% plastic strain along rolling (RD) and transverse direction (TD) at room (RT) and cryogenic temperature (-150 oC, CT) followed by annealing at 320 oC for 1 h to investigate the twinning and dislocation evolution and its consequent effect on the flow stress, plastic strain and strain hardening rate. Compared to RT-stretched samples, significant improvement in yield stress, strain hardening rate and moderate reduction in elongation to failure were witnessed for CT-stretched samples along RD and TD. The subsequent EBSD analysis revealed the increased fraction of fine {10-12} twins and nucleation of multiple {10-12} twin variants caused by higher local stress concentration at the grain boundaries in CT-stretched samples as manifested by the kernel average misorientation. This higher twin fraction and twin-twin interaction imposed the strengthening by restricting the mean free path of dislocations, leading to higher flow stress and strain hardening rate. During annealing of the RT/CT-stretched samples, the residual strain energy and twin boundaries were decreased due to static recovery, leading to a coarse-grained twin-free microstructure. Strain induced boundary migration (SBIM) was found to be the predominant mechanism governing the grain growth during annealing via movement of high angle grain boundaries.

Keywords: magnesium, twinning, twinning variant selection, EBSD, cryogenic deformation

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Authors: Silpita Paul, Susanta Sadhukhan, Biswanath Maity, Madhusudan Das

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Neural tube defects (NTDs) are one of the most common forms of birth defect and affect ~300,000 new born worldwide each year. The prevalence is higher in Northern India (11 per 1000 birth) compare to southern India (5 per 1000 birth). NTDs are one of the common birth defects related with low blood folate and Hcy concentration. Though the mechanism is still unknown, but it is now established that, NTDs in human are polygenic in nature and follow the heterogeneous trait. In spite of its heterogeneity, polymorphism in few genes affects significantly the trait of NTDs. Polymorphisms in the genes FOLH1 and MTHFR plays important role in NTDs. In this study, the polymorphisms of these genes were screened by bi-directional sequencing from 30 mothers with NTD babies as case. The result revealed that 26.67% patients had bi-allelic FOLH1 polymorphism. The polymorphism has been identified as p.Y60H and frequent to cause NTDs. The study of MTHFR gene showed 2 different SNPs rs1801131 (at exon 4) and rs1801131 (at exon 7). The study showed 6.67% patients of both mono- and bi-allelic MTHFR-rs1801131 polymorphism and 6.67% patients of bi-allelic MTHFR-rs1801131 polymorphism. These polymorphisms has been responsible for p.A222V and p.E429A change respectively and frequently involved in NTD formation. Those polymorphisms affect mainly the absorption of dietary folate from intestine and the formation of 5-methylenetetrahydrofolate (5 MTHF) from 5,10-methylenetetrahydrofolate (5,10- MTHF), which is the functional folate form in our system. Though the study is not complete yet, but these polymorphisms play crucial roles in the formation of NTDs in other world population. Based on the result till date, it can be concluded that they also play significant role in our population too as in control samples we have not found any changes.

Keywords: neural tube defects, polymorphism, FOLH1, MTHFR

Procedia PDF Downloads 283

Authors: Bernice Lottering, Yi-Wen Lin

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Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

Procedia PDF Downloads 105

Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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