Search results for: MICE tourism
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1492

Search results for: MICE tourism

652 Acupoint Injection of High Concentration of Glucose Attenuates Mice Chronic Pain and Depression Comorbidity

Authors: Chanya Inprasit, Yi-Wen Lin

Abstract:

Inflammation causes changes of peripheral and central nervous system properties, affecting both neuronal and non-neuronal cells, resulting in inflammatory pain. Acupoint injection (AI) was developed in the 1950s and has been widely used for relieving pain. It is an acupoint-stimulating technique that utilizes anatomically based meridians derived from Chinese medicine theory. AI has been accepted as an effective treatment and is thought to display superior results when compared to traditional acupuncture methods. However, the mechanism of AI needs to be ratified by more scientific evidence in order to support the theory and its therapeutic development. In this study, we explored the effect of AI on the comorbidity of chronic pain and depression. Mice hindpaw was injected by complete Freund’s adjuvant (CFA) to induce the condition of chronic pain. Measurements of mechanical and thermal hyperalgesia and depression-like behavior were analyzed. The results indicated a positive tendency to AI treatment. The comorbidity of chronic pain and depression was investigated with relation to transient receptor potential V1 (TRPV1) mechanism through the use of TRPV1 gene deletion. The expression of nociceptors such as voltage-gated sodium channels (Navs) or TRPV1, was significantly down-regulated by AI. The expression of inflammation-activated molecules: astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, and related kinases, were reversed by AI in both the peripheral and central nervous system. Taken together, these data provided a detailed molecular mechanism of AI-induced analgesia and anti-inflammatory properties. This finding may be utilized for clinical practice to treat chronic pain and depression comorbidity.

Keywords: inflammatory pain, acupoint injection, TRPV1, GFAP, S100B

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651 Factors Affecting Online Tourism Services in Israel

Authors: Shlomit Hon-Snir, Shosh Shahrabai, Sharon Teitler Regev, Anabel Friedlander-Lifszyc

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Today, online travel sites account for a large share of the orders for tourism services, leading to the expectation that many traditional travel agencies will become redundant in the future. Technological changes are offering customers a wider variety and better prices, and the improved competition in the industry has increased customer well-being significantly. Therefore, the question is whether all customers can enjoy this change, specifically whether different groups in the Israeli population enjoy the changes similarly. The purpose of this study is to identify the factors that affect the collection of data and the purchase of tourism products online and in particular to identify the barriers and limitations of technology usage among the population. The results of the current research are of great importance both economically and socially. The theory of Reasoned Action assumes that actual behavior is based on intention. Volitional behavior is predicted by individuals' attitudes to that behavior and by the way they think other people will look at them. Two cognitive variables regarding the use of technology are: perceived usefulness and perceived ease-of-use. Moreover, early adopters of innovations have different characteristics than people that adopt an innovation at a later stage. In the study, we analyze four groups of factors: Customer characteristics, internet usage, technology acceptance and product characteristics. Some of the parameters are gender, age, income level, frequency and type of internet use, proficiency in English, traveler type, number of trips abroad, perceived ease of use, perceived usefulness, perceived risk, perceived trust and product type. We investigate online purchasing and online information search separately. Data will be collected using an online questionnaire distributed among a representative sample of 600 citizens in Israel. Some of the research questions will be based on previous research studies (that underwent reliability and validity testing). Those questions will be translated into Hebrew and adjusted for the tested population.

Keywords: customer characteristics, online travel sites, technology acceptance, tourism

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650 Diagnosis on Environmental Impacts of Tourism at Caju Beach in Palmas, Tocantins, Brazil

Authors: Mary L. G. S. Senna, Veruska, C. Dutra, Jr., Keity L. F. Oliveira, Patrícia A. Santos, Alana C. M. Santana

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Environmental impacts are the changes in the physical, chemical or biological properties of natural areas that are most often caused by human actions on the environment and which have consequences for human health, society and the elements of nature. The identification of the environmental impacts is important so that they are mitigated, and above all that the mitigating measures are applied in the area. This work aims to identify the environmental impacts generated in the Praia do Caju area in the city of Palmas/Brazil and show that the lack of structure on the beach intensifies the environmental impacts. The present work was carried out having as parameter, the typologies of exploratory and descriptive and quantitative research through a matrix of environmental impacts through direct observation and registration. The study took place during the holidays from August to December 2016 and photographic record of impacts. From the collected data it was possible to verify that Caju beach suffers constant degradation due to irregular deposition.

Keywords: leisure, tourism, environmental impacts, Brazil

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649 Implementation of Cord- Blood Derived Stem Cells in the Regeneration of Two Experimental Models: Carbon Tetrachloride and S. Mansoni Induced Liver Fibrosis

Authors: Manal M. Kame, Zeinab A. Demerdash, Hanan G. El-Baz, Salwa M. Hassan, Faten M. Salah, Wafaa Mansour, Olfat Hammam

Abstract:

Cord blood (CB) derived Unrestricted Somatic Stem Cells (USSCs) with their multipotentiality hold great promise in liver regeneration. This work aims at evaluation of the therapeutic potentiality of USSCs in two experimental models of chronic liver injury induced either by S. mansoni infection in balb/c mice or CCL4 injection in hamsters. Isolation, propagation, and characterization of USSCs from CB samples were performed. USSCs were induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. Cells of the third passage were transplanted in two models of liver fibrosis: (1) Twenty hamsters were induced to liver fibrosis by repeated i. p. injection of 100 μl CCl4 /hamster for 8 weeks. This model was designed as; 10 hamsters with liver fibrosis and treated with i.h. injection of 3x106 USSCs (USSCs transplanted group), 10 hamsters with liver fibrosis (pathological control group), and 10 hamsters with healthy livers (normal control group). (2) Murine chronics S.mansoni model: twenty mice were induced to liver fibrosis with S. mansoni ceracariae (60 cercariae/ mouse) using the tail immersion method and left for 12 weeks. This model was designed as; 10 mice with liver fibrosis were transplanted with i. v. injection of 1×106 USCCs (USSCs transplanted group). Other 2 groups were designed as in hamsters model. Animals were sacrificed 12 weeks after USSCs transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemistry staining. Moreover, liver sections were examined for fibrosis level, and fibrotic indices were calculated. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes. In both animal models, in vitro induced hepatocyte-like cells were confirmed by cytoplasmic expression of glycogen, alpha-fetoprotein, and cytokeratin18. Livers of USSCs transplanted group showed engraftment with human hepatocyte-like cells as proved by cytoplasmic expression of human alpha-fetoprotein, cytokeratin18, and OV6. In addition, livers of this group showed less fibrosis than the pathological control group. Liver functions in the form of serum AST & ALT level and serum total bilirubin level were significantly lowered in USSCs transplanted group than pathological control group (p < 0.001). Moreover, the fibrotic index was significantly lower (p< 0.001) in USSCs transplanted group than pathological control group. In addition liver sections, of i. v. injection of 1×106 USCCs of mice, stained with either H&E or sirius red showed diminished granuloma size and a relative decrease in hepatic fibrosis. Our experimental liver fibrosis models transplanted with CB-USSCs showed liver engraftment with human hepatocyte-like cells as well as signs of liver regeneration in the form of improvement in liver function assays and fibrosis level. These data provide hope that human CB- derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis.

Keywords: cord blood, liver fibrosis, stem cells, transplantation

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648 A Theragnostic Approach for Alzheimer’s Disease Focused on Phosphorylated Tau

Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

Abstract:

Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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647 The Impact of Intercultural Communicative Competence on the Academic Achievement of English Language Learners: Students Working in the Sector of Tourism in Jordan (Petra and Jerash) as a Case Study

Authors: Haneen Alrawashdeh, Naciye Kunt

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Intercultural communicative competence or (ICC), is an extension of communicative competence that takes into account the intercultural aspect of learning a foreign language. Accordingly, this study aimed at investigating the intercultural interaction impact on English as a foreign language learners' academic achievement of language as a scholastic subject and their motivation towards learning it. To achieve the aim of the study, a qualitative research approach was implemented by means of semi-structured interviews. Interview sessions were conducted with eight teachers of English as well as ten English language learners who work in the tourism industry in a variety of career paths, such as selling antiques and traditional costumes. An analysis of learners' grades of English subjects from 2014 to 2019 academic years was performed by using the Open Education Management Information System Database in Jordan to support the findings of the study. The results illustrated that due to the fact that they work in the tourism sector, students gain skills and knowledge that assist them in better academic achievement in the subject of English by practicing intercultural communication with different nationalities on a daily basis; intercultural communication enhances students speaking skills, lexicon, and fluency; however, despite that their grades showed increasing, from teachers perspectives, intercultural communicative competence reduces their linguistic accuracy and ability to perform English academic writing in academic contexts such as exams.

Keywords: intercultural communicative competence, Jordan, language learning motivation, language academic achievement

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646 The Effects of Acupoint Catgut Embedding for Weight Control in Mice Model

Authors: Chanya Inprasit, Ching-Liang Hsieh, Yi-Wen Lin

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Obesity (OB) is a hazardous global health problem that has been increasing in prevalence, more severely in last decade. It is the mainly resultant from the imbalance between food consumption and energy expenditure, which is concordant with a modern lifestyle, implying an increase in calories with poorer quality of food intake accompanied by a decrease in physical activities. Obesity does not concern the appearance only but is also a major factor contributing to poor physiology, psychology, society and economic issues. Moreover, OB induces low-grade inflammation in the body through the regulatory effect it enacts on the adipocyte function. Various alternative treatments were investigated for body weight control, including Acupoint Catgut Embedding (ACE). ACE is the implantation of absorbable catgut sutures at specific acupoints, displaying durable and potent stimulation and thereby reducing the treatment frequency. Our study utilized a mouse model to exclude any psychological factors of OB and ACE treatment. High-fat diet and body weight were measured once a week before subjects in ACE and Sham group received the ACE treatment or placebo treatment. We hypothesized that ACE can control body weight through the interaction of the TRPV1 pathways, as TRPV1 accordingly responds to inflammatory factors. The results of body weight variation show a significant decrease in body weight in ACE group compared with the baseline of control and Sham group. Meanwhile, converse results were explored in TRPV1 knockout mice, where a significant maintenance of normal body weight throughout the experiment period was observed. There was no significant difference in food consumption of each group. These finding indicated that TRPV1 pathways and its associated pathways may be involved in the maintenance of body weight, which can be controlled by ACE treatment of genetic manipulation.

Keywords: acupoint catgut embedding, obesity, hypothalamus, TRPV1

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645 Sustainable Development of an Insular Region: Heritage and Identity Enhancement of Kerkennah Islands

Authors: Houda Kohli Kallel, Soumaya Gharsallah Falhi

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Kerkennah Islands are a group of islands lying off the eastern coast of Tunisia, 15 miles from the Sfaxian coast. This archipelago covers an area of 150 square kilometres, and it consists of two main islands : The Gharbi and The Chergui . It also covers twelve more islets. Kerkennah is endowed with an exceptional cultural, natural and ecological potential, essential for the sustainability of the island community. Hence ,the inhabitants there have mobilized the natural resources of their land for decades. However, today, and despite these heritage treasures, Kerkennian islanders are facing social, economic and environmental challenges which are currently hindering the development of the traditional activities of fishing and farming. Other than being isolated and having a non-diversified economy, we cite the erosion of the stream banks, the exodus of young people and the population aging. "This study find the solutions that are likely to allow a sustainable development of the island territory, its enhancement and the strengthening of its identity. It is also necessary to study the key factors impacting the archipelago’s cultural tourism of decision makers and citizens. First, we will present the archipelago. Second, we will describe its tangible as well as intangible heritage. Then, we will present the new modes of the site exploitation. Finally, we will identify some new projects paving the way to a sustainable tourism in Kerkennah such as Borj EL Lahssar archaeological digs and Kerkennah insular heritage museum. To conclude, the archipelago of Kerkennah needs to reintegrate all its historical, architectural and archaeological assets in order to enhance its cultural tourism based on the cultural circuits of the territorial identities and the island values.

Keywords: kerkennah, identity, heritage, historical architectural

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644 The Senior Traveler Market as a Competitive Advantage for the Luxury Hotel Sector in the UK Post-Pandemic

Authors: Feyi Olorunshola

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Over the last few years, the senior travel market has been noted for its potential in the wider tourism industry. The tourism sector includes the hotel and hospitality, travel, transportation, and several other subdivisions to make it economically viable. In particular, the hotel attracts a substantial part of the expenditure in tourism activities as when people plan to travel, suitable accommodation for relaxation, dining, entertainment and so on is paramount to their decision-making. The global retail value of the hotel as of 2018 was significant for tourism. But, despite indications of the hotel to the tourism industry at large, very few empirical studies are available to establish how this sector can leverage on the senior demographic to achieve competitive advantage. Predominantly, studies on the mature market have focused on destination tourism, with a limited investigation on the hotel which makes a significant contribution to tourism. Also, several scholarly studies have demonstrated the importance of the senior travel market to the hotel, yet there is very little empirical research in the field which has explored the driving factors that will become the accepted new normal for this niche segment post-pandemic. Giving that the hotel already operates in a highly saturated business environment, and on top of this pre-existing challenge, the ongoing global health outbreak has further put the sector in a vulnerable position. Therefore, the hotel especially the full-service luxury category must evolve rapidly for it to survive in the current business environment. The hotel can no longer rely on corporate travelers to generate higher revenue since the unprecedented wake of the pandemic in 2020 many organizations have invented a different approach of conducting their businesses online, therefore, the hotel needs to anticipate a significant drop in business travellers. However, the rooms and the rest of the facilities must be occupied to keep their business operating. The way forward for the hotel lies in the leisure sector, but the question now is to focus on the potential demographics of travelers, in this case, the seniors who have been repeatedly recognized as the lucrative market because of increase discretionary income, availability of time and the global population trends. To achieve the study objectives, a mixed-method approach will be utilized drawing on both qualitative (netnography) and quantitative (survey) methods, cognitive and decision-making theories (means-end chain) and competitive theories to identify the salient drivers explaining senior hotel choice and its influence on their decision-making. The target population are repeated seniors’ age 65 years and over who are UK resident, and from the top tourist market to the UK (USA, Germany, and France). Structural equation modelling will be employed to analyze the datasets. The theoretical implication is the development of new concepts using a robust research design, and as well as advancing existing framework to hotel study. Practically, it will provide the hotel management with the latest information to design a competitive marketing strategy and activities to target the mature market post-pandemic and over a long period.

Keywords: competitive advantage, covid-19, full-service hotel, five-star, luxury hotels

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643 Professional Management on Ecotourism and Conservation to Ensure the Future of Komodo National Park

Authors: Daningsih Sulaeman, Achmad Sjarmidi, Djoko T. Iskandar

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Komodo National Park can be associated with the implementation of ecotourism program. The result of Principal Components Analysis is synthesized, tested, and compared to the basic concept of ecotourism with some field adjustments. Principal aspects of professional management should involve ecotourism and wildlife welfare. The awareness should be focused on the future of the Natural Park as 7th Wonder Natural Heritage and its wildlife components, free from human wastes and beneficial to wildlife and local people. According to perceptions and expectations of visitors from various results of tourism programs, the visitor’s perceptions showed that the tourism management in Komodo National Park should pay more attention to visitor's satisfaction and expectation and gives positive impact directly to the ecosystem sustainability, local community and transparency to the conservation program.

Keywords: 7th wonders of nature, ecotourism, Komodo dragon, visitor’s perceptions, wildlife management

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642 Evaluation of Anticonvulsant and Sedative-Hypnotic Activities of Novel 2-Fluorobenzyloxy 4,6- Diphenylpyrimidin-2-Ol Derivatives in Mice

Authors: Golnar Hasheminasab, Mehrdad Faizi, Mona Khoramjouy

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Introduction: Benzodiazepines (BZDs) have pharmacological effects, including anxiolytic, sedative-hypnotic, anticonvulsant, and muscle relaxant properties. However, they have adverse effects such as interaction with alcohol, ataxia, impaired learning, and psychological and physical dependence. According to the structure of zolpidem and on the basis of the structure-activity relationship of BZD receptor ligands, six novel derivatives of 2-fluorobenzyloxy 4,6- diphenylpyramidin-2-ol have been synthesized. We studied the hypnotic, sedative, and anticonvulsant effects of the novel compounds. Method: In this study, we used male mice (18 to 25 g). All the substances were injected intraperitoneally. The hypnotic effect of the compounds was examined by pentobarbital induced sleeping test. The locomotor activities and sedative effects of the novel compounds were evaluated by open field and loss of righting reflex test, respectively. The anticonvulsant effects of the novel compounds were assessed by PTZ and MES tests. Results: In the pentobarbital induced sleeping and open field tests, compound 4-(2-((2-fluorobenzyl)oxy)phenyl)-6-(p-tolyl) pyrimidine-2-ol with ED50=14.20 mg/kg and ED50=47.88 mg/kg, respectively, was the most effective compound. None of the novel compounds showed a significant anticonvulsant effect in the PTZ test. In MES test, compound 4-(2-((2-fluorobenzyl)oxy)phenyl)-6-(p-tolyl)pyrimidine-2-ol with ED50=12.92 mg/kg was the most effective compound. Flumazenil blocked the sedation and hypnosis of all the compounds. Conclusion: All of the novel derivatives showed significant sedative-hypnotic activities and caused the reduction of locomotor activities. The results show that the methyl lipophilic substitutes on the phenyl ring of 4,6-diphenylpyramidin-2-ol derivatives can increase the sedative and hypnotic effects of the derivatives. Flumazenil antagonized the sedative, and the hypnotic effects of the compounds indicate that BZD receptors are involved in the effects.

Keywords: BZD, sedative, hyptonic, anticonvulsant, zolpidem, MES, PTZ, benzodiazepine, locomotor activities, pentobarbital induced sleeping tests

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641 Digital And Technological Transformation of Cappadocia Valleys: Kizilçukur, Meskendi̇r, Güllüdere 1, Güllüdere 2

Authors: Şenay Güngör, Emre Elbaşi, Beyda Sadikğlu, Utku Eren Bağci, Ömer Uzunel

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One of the first places that comes to mind when it comes to tourism in Turkey is the Cappadocia Region. Due to its rich geological and geomorphological heritage, Cappadocia is one of the most visited destinations in the world. In fact, in the first half of 2023, the number of international tourists visiting Cappadocia exceeded 2 million. Considering that the economy of the Cappadocia region is largely based on tourism, it is understood that the quality and technology integration levels of the touristic services offered in the region are of great importance. In this context; as a result of the observations made in Kızılçukur, Meskendir, Güllüdere 1 and Güllüdere 2 valleys, where the important hiking routes of the Cappadocia Region are located, it has been observed that the digital level of the routes is insufficient. It has been observed that the telephone networks in the area are very low or have completely lost their signal strength. In addition, it was determined that the materials such as maps and brochures used by tourism agencies to introduce the valleys are simple and incomplete. It is thought that this situation negatively affects the tourists' orientation and touristic experience in the field. Eliminating these deficiencies identified in the field, improving the digital level of the above-mentioned hiking routes and increasing the added value in destinations are among the main objectives of our study. Within the scope of the study, a mobile application that can work both online and offline on hiking routes has been prepared. 3D modeling of Kızılçukur, Meskendir, Güllüdere 1 and Güllüdere 2 valleys were made using Geographical Information Systems (GIS). In addition, a website has been created to enable tourists to easily access all the above-mentioned information, visuals and technological applications related to the routes. As it is known, the effective use of information and communication technologies in touristic regions not only increases the satisfaction levels of tourists, but also positively affects the attraction of qualified tourists to the region. When the tangible and intangible outputs of this study are evaluated, it is thought that it will serve the social and economic development of the region and set an example for the digital transformation of other routes in the region.

Keywords: nevşehir, cappadocia, cappadocia valleys, tourism route

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640 Cryptocurrency as a Payment Method in the Tourism Industry: A Comparison of Volatility, Correlation and Portfolio Performance

Authors: Shu-Han Hsu, Jiho Yoon, Chwen Sheu

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With the rapidly growing of blockchain technology and cryptocurrency, various industries which include tourism has added in cryptocurrency as the payment method of their transaction. More and more tourism companies accept payments in digital currency for flights, hotel reservations, transportation, and more. For travellers and tourists, using cryptocurrency as a payment method has become a way to circumvent costs and prevent risks. Understanding volatility dynamics and interdependencies between standard currency and cryptocurrency is important for appropriate financial risk management to assist policy-makers and investors in marking more informed decisions. The purpose of this paper has been to understand and explain the risk spillover effects between six major cryptocurrencies and the top ten most traded standard currencies. Using data for the daily closing price of cryptocurrencies and currency exchange rates from 7 August 2015 to 10 December 2019, with 1,133 observations. The diagonal BEKK model was used to analyze the co-volatility spillover effects between cryptocurrency returns and exchange rate returns, which are measures of how the shocks to returns in different assets affect each other’s subsequent volatility. The empirical results show there are co-volatility spillover effects between the cryptocurrency returns and GBP/USD, CNY/USD and MXN/USD exchange rate returns. Therefore, currencies (British Pound, Chinese Yuan and Mexican Peso) and cryptocurrencies (Bitcoin, Ethereum, Ripple, Tether, Litecoin and Stellar) are suitable for constructing a financial portfolio from an optimal risk management perspective and also for dynamic hedging purposes.

Keywords: blockchain, co-volatility effects, cryptocurrencies, diagonal BEKK model, exchange rates, risk spillovers

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639 Sustainable Marine Tourism: Opinion and Segmentation of Italian Generation Z

Authors: M. Bredice, M. B. Forleo, L. Quici

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Coastal tourism is currently facing huge challenges on how to balance environmental problems and tourist activities. Recent literature shows a growing interest in the issue of sustainable tourism from a so-called civilized tourists’ perspective by investigating opinions, perceptions, and behaviors. This study investigates the opinions of youth on what makes them responsible tourists and the ability of coastal marine areas to support tourism in future scenarios. A sample of 778 Italians attending the last year of high school was interviewed. Descriptive statistics, tests, and cluster analyses are applied to highlight the distribution of opinions among youth, detect significant differences based on demographic characteristics, and make segmentation of the different profiles based on students’ opinions and behaviors. Preliminary results show that students are largely convinced (62%) that by 2050 the quality of coastal environments could limit seaside tourism, while 10% of them believe that the problem can be solved simply by changing the tourist destination. Besides the cost of the holiday, the most relevant aspect respondents consider when choosing a marine destination is the presence of tourist attractions followed by the quality of the marine-coastal environment, the specificity of the local gastronomy and cultural traditions, and finally, the activities offered to guests such as sports and events. The reduction of waste and lower air emissions are considered the most important environmental areas in which marine-coastal tourism activities can contribute to preserving the quality of seas and coasts. Areas in which, as a tourist, they believe possible to give a personal contribution were (responses “very much” and “somewhat”); do not throw litter in the sea and on the beach (84%), do not buy single-use plastic products (66%), do not use soap or shampoo when showering in beaches (53%), do not have bonfires (47%), do not damage dunes (46%), and do not remove natural materials (e.g., sand, shells) from the beach (46%). About 6% of the sample stated that they were not interested in contributing to the aforementioned activities, while another 7% replied that they could not contribute at all. Finally, 80% of the sample has never participated in voluntary environmental initiatives or citizen science projects; moreover, about 64% of the students have never participated in events organized by environmental associations in marine or coastal areas. Regarding the test analysis -based on Kruskal-Wallis and Mann and Whitney tests - gender, region, and studying area of students reveals significance in terms of variables expressing knowledge and interest in sustainability topics and sustainable tourism behaviors. The classification of the education field is significant for a great number of variables, among which those related to several sustainable behaviors that respondents declare to be able to contribute as tourists. The ongoing cluster analysis will reveal different profiles in the sample and relevant variables. Based on preliminary results, implications are envisaged in the fields of education, policy, and business strategies for sustainable scenarios. Under these perspectives, the study has the potential to contribute to the conference debate about marine and coastal sustainable development and management.

Keywords: cluster analysis, education, knowledge, young people

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638 Music Tourism for Identity and Cultural Communication in Qualitative Analysis with MAXQDA

Authors: Yixuan Peng

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Music tourism is the phenomenon of people visiting a place because of their association with music, as well as the process of creating an emotional attachment to a place through the connection between people and music. Music offers people the opportunity to immerse themselves in the local culture. Music tourism is increasingly recognized as an industry with economic and social impacts. People often come together for a common purpose of music at a certain time and place, such as concert, opera, or music workshop. This is very similar to the act of pilgrimage: the process of participation evokes strong emotions; it takes time and money to get to the destination; the gathering, and the emotional co-frequency. This study conducted further qualitative research using MAXQDA by applying the musical topophilia model with East Asians as interview subjects. There are three steps to traveling: before, during and after the trip. To date, 53 individuals living in East Asia have been interviewed one-on-one (online/offline) about their travel experiences. This part of the interview is limited to the two stages that are before and after travel. Based on the results of the interviews above, and as Europe has the most representative music industry and the richest variety of music genres. The " during the trip" phase of the observations and interviews were conducted in Europe and involved on-site music in Salzburg and London, including musical theater, street music, and musical pilgrimages. Interviews with 24 people were conducted in English, Chinese and Japanese. This study will use data to demonstrate the followings: the irreplaceability of music in faraway places; the identity and sense of belonging that music brings; the ethnic barriers that music crosses; and the cultural communication that music enables.

Keywords: belongingness, gathering, modern pilgrimage, anthropology of music, sociology of music

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637 Exploring the Effects of Cuisine Experience, Emotions, Place Attachment on Heritage Tourists’ Revisit Behavioral Intentions: The Case Study of Lu-Kang

Authors: An-Na Li, Ying-Yu Chen, Yu-Lung Lin

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Food tourism is one of the growing industries in the tourism industry today. The Destination Marketing Organizations (DMOs) are aware of the importance of gastronomy to stimulate local and regional economic development. From the heritage and cultural aspects, gastronomy is becoming a more important part of the cultural heritage of the region. Heritage destinations provide culinary heritage, which fits the current interest in traditional food, and cuisine is a part of a general desire for authentic experience. However, few studies have empirically examined antecedents of food tourists’ behavioral intentions. This study examined the effects of cuisine experience; emotions, place attachment and tourists’ revisit behavioral intentions. A total of 408 individuals responded to the on-site survey in the historic town of Lu-Kang in Taiwan. The results indicated that tourists’ cuisine experience include place flavor, media recommendation, local learning, life transfer and interpersonal share. In addition, cuisine experience had significant impacts on emotions and place attachment, emotions had significant effects on place attachment, furthermore, which in turn place attachment had significant effects on tourists’ revisit behavioral intentions. The findings suggested that the cuisine experience is a multi-dimensions construct. On the other hands, the good quality of cuisine experience could evoke tourists’ positive emotions and it could play a significant role in promoting tourist revisit intentions or word of mouth. Implications for theory and practice are discussed.

Keywords: culinary tourism, cuisine experiences, emotions, revisit intentions

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636 A User Study on the Adoption of Context-Aware Destination Mobile Applications

Authors: Shu-Lu Hsu, Fang-Yi Chu

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With the advances in information and communications technology, mobile context-aware applications have become powerful marketing tools. In Apple online store, there are numerous mobile applications (APPs) developed for destination tour. This study investigated the determinants of adoption of context-aware APPs for destination tour services. A model is proposed based on Technology Acceptance Model and privacy concern theory. The model was empirically tested based on a sample of 259 users of a tourism APP published by Kaohsiung Tourism Bureau, Taiwan. The results showed that the fitness of the model is well and, among all the factors, the perceived usefulness and perceived ease of use have the most significant influences on the intention to adopt context-aware destination APPs. Finally, contrary to the findings of previous literature, the effect of privacy concern on the adoption intention of context-aware APP is insignificant.

Keywords: mobile application, context-aware, privacy concern, TAM

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635 Enhancing Mitochondrial Activity and Metabolism in Aging Female Germ Cells: Synergistic Effects of Dual ROCK and ROS Inhibition

Authors: Kuan-Hao Tsui, Li-Te Lin, Chia-Jung Li

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The combination of Y-27632 and Vitamin C significantly enhances the quality of aging germ cells by reducing reactive oxygen species (ROS) production, restoring mitochondrial membrane potential balance, and promoting mitochondrial fusion. The age-related decline in oocyte quality contributes to reduced fertility, increased aneuploidy, and diminished embryo quality, with mitochondrial dysfunction in both oocytes and granulosa cells being a key factor in this decline. Experiments on aging germ cells investigated the effects of the Y-27632 and Vitamin C combination. In vivo studies involved aged mice to assess oocyte maturation and ROS accumulation during culture. The assessment included mitochondrial activity, ROS levels, mitochondrial membrane potential, and mitochondrial dynamics. Cellular energy metabolism and ATP production were also measured. The combination treatment effectively addressed mitochondrial dysfunction and regulated cellular energy metabolism, promoting oxygen respiration and increasing ATP production. In aged mice, this supplement treatment enhanced in vitro oocyte maturation and prevented ROS accumulation in aging oocytes during culture. While these findings are promising, further research is needed to explore the long-term effects and potential side effects of the Y-27632 and Vitamin C combination. Additionally, translating these findings to human subjects requires careful consideration. Overall, the study suggests that the Y-27632 and Vitamin C combination could be a promising intervention to mitigate aging-related dysfunction in germ cells, potentially enhancing oocyte quality, particularly in the context of in vitro fertilization.

Keywords: ovarian aging, supplements, ROS, mitochondria

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634 Exploring Tourist’s Attitude towards Environmentally Friendly Practices

Authors: René Haarhoff

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Consumers are constantly reminded of their responsibility towards the environment in a world where words such as global warming, carbon footprint, recycling or ‘green’’ everything has become common language. What was previously considered to be ordinary practices are in many instances frowned upon today and consumers are expected to individually contribute towards a greener mother earth. However unused recycle bins, single travelers in luxury cars, busy airports and vast deforested areas for new developments tell another story. The question arises whether the everyday man in the street really takes the responsibility to balance the three pillars of sustainability: the planet, its people and profit. Undeniably our activities impact on the environment where a healthy economy is needed in a fast paced global environment. The situation is further gloomed in instances where the consumer has paid for inclusive services which directly impacts on the environment. A prime example of this is the tourism industry: accommodation establishments or resorts include clean, daily washed towels and bedding, large bath tubs, inclusive use of electricity and water to name a few. This research evaluates environmentally friendly practices consumers follow at home and also when on holiday. Respondents at Bloemfontein airport, often using tourism products were included in the study. Results reveal that the majority of respondents state that they are concerned about the environment yet when questioned on donation towards endangered species, switching off lights in hotel rooms or using water sparingly a significant difference in results are evident. From the research results it is evident that consumers do not practice what they preach towards a greener environment.

Keywords: green, environment, consumer, tourism, sustainable practices

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633 The Influence of Online Marketing Tactics in Tourist Destination Reputation: Egypt as a Case Study

Authors: Alyaa Darwish, Peter Burns, Sofia Reino

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Online marketing has been the key focus of attention for the majority of destinations since the Internet became the primarily information tool for travel marketing. Tourism is a reputation-dependent industry; potential travelers who do not have previous experience with the destination face numerous risks during the process of decision-making. An accurate perception of the destination’s reputation helps to minimize risk against unsatisfying travel experiences. However, there has been limited investigation with regards to the reputation of tourist destination. Taking the importance of reputation to the tourism industry, this research aims to: 1) Develop a destination reputation model; 2) Assess the tourist destination approach towards online marketing tactics; 3) Evaluate the impact of differentiated online marketing tactics on reputation; and 4) Measure the potential for using online marketing tactics to manage the destination’s online reputation. This research follows an interpretivism epistemological research approach through using four research methods; interviews, questionnaire, content analysis, and experiment to achieve the research goals.

Keywords: destination reputation, online marketing, reputation, tactics

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632 Effect of Cardio-Specific Overexpression of MUL1, a Mitochondrial Protein on Myocardial Function

Authors: Ximena Calle, Plinio Cantero-López, Felipe Muñoz-Córdova, Mayarling-Francisca Troncoso, Sergio Lavandero, Valentina Parra

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MUL1, a mitochondrial E3 ubiquitin ligase anchored to the outer mitochondrial membrane, is highly expressed in the heart. MUL1 is involved in multiple biological pathways associated with mitochondrial dynamics. Increased MUL1 affects the balance between fission and fusion, affecting mitochondrial function, which plays a crucial role in myocardial function. Therefore, it is interesting to evaluate the effect of cardiac-specific overexpression of MUL1 on myocardial function. Aim: To determine heart functionality in a mouse model with cardio-specific overexpression MUL1 protein. Methods and Results: Male C57BL/Tg transgenic mice with cardiomyocyte-specific overexpression of MUL1 (n=10) and control (n=4) were evaluated at 12, 27, and 35 weeks of age. Glucose tolerance curve determination was performed after a 6-hours fast to assess metabolic capacity, treadmill test, and systolic, and diastolic pressure was evaluated by the mouse tail-cuff blood pressure system equipment. The result showed no glucose tolerance curve, and the treadmill test demonstrated no significant changes between groups. However, substantial changes in diastolic function were observed by ultrasound and determination of cardiac hypertrophy proteins by western blot. Conclusions: Cardio-specific overexpression of MUL1 in mice without any treatment affects diastolic cardiac function, thus showing the important role contributed by MUL1 in the heart. Future research should evaluate the effect of cardiomyocyte-specific overexpression of MUL1 in pathological conditions such as a high-fat diet is one of the main risk factors for cardiovascular disease.

Keywords: diastolic dysfunction, hypertrophy cardiac, mitochondrial E3 ubiquitin ligase 1, MUL1

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631 Regenerative Therapeutic Effect of Statin Nanoparticle-Loaded Adipose-Derived Stem Cells on Myocardial Infarction

Authors: Masaaki Ii, Takashi Saito, Yasuhiko Tabata, Shintaro Nemoto

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Background: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI). Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups 3 days after MI: 1) PBS (control), 2) NP-AdSCs (50000 cells), 3) STNP, and 4) STNP-AdSCs (50000 cells). Cardiac functional recovery assessed by echocardiography was improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that LV fibrosis length was reduced, and the number of TUNEL-positive cardiomyocytes was less in STNP-AdSC group. Surprisingly, a number of de novo endogenous Nkx-2.5/GATA4 positive immature cardiomyocytes as well as massive vascular formation were observed in outer layer of infarcted myocardium despite of a few recruited/retained transfused STNP-AdSCs 4 weeks after MI in STNP-AdSC group. Finally, massive myocardial regeneration was observed 8 weeks after MI. Conclusions: Intravenously injected small number of statin nanoparticle-loaded hAdSCs exhibited a potent therapeutic effect inducing endogenous cardiac tissue regeneration.

Keywords: statin, drug delivery system, stem cells, cardiac regeneration

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630 The Dual Role of the Internet in the Development of Local Communities Through Ecotourism and Cultural Assimilation in Iran

Authors: Haniyeh Sameie

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In the process of globalization, geographical boundaries gradually lose their importance, and ethnic, local, and regional cultures are integrated with each other and even marginalized. Globalization has many manifestations and aspects, including economic, political, social, etc., but this paper has focused on the cultural aspect of globalization. From this point of view, one of the important issues that have always been raised is the assimilation of diverse and plural cultures, which are gradually disappearing and destroyed in the onslaught of global culture and are dissolved in global culture. In the postmodern paradigm, the tools of the globalized world can be used to preserve and strengthen cultural diversity. For example, the Internet, as a globalization tool, can play an important role in preserving and recognizing local cultures. In today's world, the world nations and ethnic groups are trying to revive their specific and native cultures in different ways in opposition to the rising cultural assimilation and challenge the globalization of culture. One of the manifestations of these actions is addressing the issue of tourism and, specifically, eco-tourism, which is being developed in Iran as well as in other parts of the world, relying on the powerful tool of globalization, the Internet. Considering the significant growth of the ecotourism industry in Iran in recent years, this paper focuses on the role of the Internet in the development of ecotourism in Iran as one of the manifestations of tourism in recent decades and how to preserve and survive diverse local cultures and strengthen local communities against global culture through it. One of the major challenges in the development of communication technology in Iran in the last decade has been the debate over the necessity or non-necessity of access to high-speed Internet in the villages of Iran. Some believe that accessing the broadband internet in the villages may lead to the disappearance of local cultures and can facilitate the spread of western culture among villagers. On the other hand, the speed of expansion of ecotourism in Iran in the last ten years is owed to the development of the Internet in villages. In this regard, we pay attention to the dual role of the Internet in cultural assimilation and, at the same time, the platform that the online space has created for the growth and development of ecotourism accommodations as a source of stable income for local communities, focusing on the Iranian experience in the recent decade.

Keywords: tourism, globalization, internet, ecotourism in Iran, cultural assimilation

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629 Reduction of Transient Receptor Potential Vanilloid 1 for Chronic Pain and Depression Co-Morbidity through Electroacupuncture and Gene Deletion in Mice Brain

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

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628 The Sustainable Development for Coastal Tourist Building

Authors: D. Avila

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The tourism industry is a phenomenon that has become a growing presence in international socio-economic dynamics, which in most cases exceeds the control parameters in the various environmental regulations and sustainability of existing resources. Because of this, the effects on the natural environment at the regional and national levels represent a challenge, for which a number of strategies are necessary to minimize the environmental impact generated by the occupation of the territory. The hotel tourist building and sustainable development in the coastal zone, have an important impact on the environment and on the physical and psychological health of the inhabitants. Environmental quality associated with the comfort of humans to the sustainable development of natural resources; applied to the hotel architecture this concept involves the incorporation of new demands on all of the constructive process of a building, changing customs of developers and users. The methodology developed provides an initial analysis to determine and rank the different tourist buildings, with the above it will be feasible to establish methods of study and environmental impact assessment. Finally, it is necessary to establish an overview regarding the best way to implement tourism development on the coast, containing guidelines to improve and protect the natural environment. This paper analyzes the parameters and strategies to reduce environmental impacts derived from deployments tourism on the coast, through a series of recommendations towards sustainability, in the context of the Bahia de Banderas, Puerto Vallarta, Jalisco. The environmental impact caused by the implementation of tourism development, perceived in a coastal environment, forcing a series of processes, ranging from the identification of impacts, prediction and evaluation of them. For this purpose are described below, different techniques and valuation procedures: Identification of impacts. Methods for the identification of damage caused to the environment pursue general purpose to obtain a group of negative indicators that are subsequently used in the study of environmental impact. There are several systematic methods to identify the impacts caused by human activities. In the present work, develops a procedure based and adapted from the Ministry of works public urban reference in studies of environmental impacts, the representative methods are: list of contrast, arrays, and networks, method of transparencies and superposition of maps.

Keywords: environmental impact, physical health, sustainability, tourist building

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627 Sustainability of Heritage Management in Aksum: Focus on Heritage Conservation and Interpretation

Authors: Gebrekiros Welegebriel Asfaw

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The management of the fragile, unique and irreplaceable cultural heritage from different perspectives is becoming a major challenge as important elements of culture are vanishing throughout the globe. The major purpose of this study is to assess how the cultural heritages of Aksum are managed for their future sustainability from heritage conservation and interpretation perspectives. Descriptive type of research design inculcating both quantitative and qualitative research methods is employed. Primary quantitative data was collected from 189 respondents (19 professionals, 88 tourism service providers and 82 tourists) and interview was conducted with 33 targeted informants from heritage and related professions, security employees, local community, service providers and church representatives by applying probability and non probability sampling methods. Findings of the study reveal that the overall sustainable management status of the cultural heritage of Aksum is below average. It is found that the sustainability of cultural heritage management in Aksum is facing a lot of unfavorable factors like lack of long term planning, incompatible system of heritage administration, limited capacity and number of professionals, scant attention to community based heritage and tourism development, dirtiness and drainage problems, problems with stakeholder involvement and cooperation, lack of organized interpretation and presentation systems and others. So, re-organization of the management system, creating platform for coordination among stakeholders and developing appropriate interpretation system can be good remedies. Introducing community based heritage and tourism development concept is also recommendable for a long term win-win success in Aksum.

Keywords: Aksum, conservation, interpretation, Sustainable Cultural Heritage Management

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626 Development of Monoclonal Antibodies against the Acute Hepatopancreatic Necrosis Disease Toxins

Authors: Naveen Kumar B. T., Anuj Tyagi, Niraj Kumar Singh, Visanu Boonyawiwat, Shanthanagouda A. H., Orawan Boodde, Shankar K. M., Prakash Patil, Shubhkaramjeet Kaur

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Since 2009, Acute Hepatopancreatic Necrosis Disease (AHPND) outbreaks have increased rapidly, and these have led to the major economic losses to the global shrimp industry. In comparison to other treatments, passive immunity and monoclonal antibody (MAb) based farmer level kit have proved their importance in controlling and treating the diseases in the shrimp industry. In the present study, MAbs were produced against the recombinant PirB protein Vibrio parahaemolyticus strain causing AHPND. Briefly, Balb/C mice were immunized with rPirB at 15 days interval, and antibody titer was determined by ELISA. Spleen cells from mice showing high antibody titer were fused with SP2O myeloma cells for hybridoma production. Among 130 hybridomas, four showed high antibody titer and positive reactivity in an immunoblot assay. In Western blot assay, three out of four MAbs (4C4, 2C2 and 4G3) showed reactivity to rPirB protein. However, in the natural host, only Mab clone 4G3 show strong reactivity (with a strain of V. parahemolyticus causing EMS/AHPND). These clones also showed reactivity with less than 20 kDa proteins in AHPND free V. parahaemolyticus (Thailand stain). Further, on from MAb 4G3 clone, four panels of single cell MAbs clones (G3F5, G3B8, G3H2, and G3D6) were produced of which three showed strong positive reactivity to rPirB protein in the Western blot. These MAbs have potential for controlling and prevention of the AHPND through passive immunity and development of filed level rapid diagnostic kits.

Keywords: shrimp, economic loss, AHPND, MAb

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625 The Role of Online Platforms in Economic Growth and the Introduction of Local Culture in Tourist Areas

Authors: Maryam Nzari

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Today, with the advancement of Internet technology, one of the tools used by humans is a tool that allows them to do what they need easily. Online platforms in different forms and by providing different services make it possible for users to communicate with each other and users with platforms. Audience communication with mass media is not the same as in the past. Today the conditions are different; With online platforms that provide the latest news minute by minute, he has access to all the content and can choose more quickly and easily. According to professionals Galloway, Apple, Amazon, Facebook and Google companies create a wide range. They are among the products and services that are connected with the daily life of billions of people all over the planet. Over time, platforms gain high economic value and in this way gain power that will influence the social, cultural, economic and political aspects of people’s lives. As a result of the effects of the process of platformization on all areas of individual and collective life, we now live in a platform society, which communicates It is close to “platform politics”. Nowadays, with social media platforms, users can interact with many people and people can share their data on various topics with others in this space. In this research, what will be investigated is the role of these online platforms in economic growth and the introduction of local culture areas in tourist areas. Tourism in a region is linked with various factors; One of the important factors that attract tourists to a region is its culture, and on the other hand, this culture can also affect economic growth. Without a proper understanding of the culture of these tourist areas, it is not possible to plan properly for the growth of the tourism industry and the subsequent increase in economic growth. The interaction of local people and tourists will have social and cultural effects on each other and will give them the opportunity to get to know each other. Therefore, the purpose of this research is to examine issues such as the role that online platforms play in cultural interaction in tourist areas and to understand that online platforms are only seeking to show the good aspects of a region and then generate enough extra income or that platforms can They play a role beyond what we imagine and introduce the culture of a region in a proper way so that we don’t see disagreements in the tourism planning of that region. in this article It has been tried by using library and field methods Answer the questions.

Keywords: online platforms, economic growth, culture Indigenous, tourism

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624 Switchable Lipids: From a Molecular Switch to a pH-Sensitive System for the Drug and Gene Delivery

Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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623 Investigation into the Phytochemistry and Biological Activities of Medicinal Plants Used in Algerian Folk Medicine: Potential Use in Human Medicine

Authors: Djebbar Atmani, Dina Kilani, Tristan Richard

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Medicinal plants are an important source for the discovery of potential new substances for use in medicine and food. Pistacia lentiscus, Fraxinus angustifolia and Clematis flammula, plants growing in the Mediterranean basin, are widely used in traditional medicine. Therefore, the present study was designed to investigate their antioxidant, anti-inflammatory, antidiabetic, anti-mutagenic/genotoxic and neuroprotective potential and identification of active compounds using appropriate methodology. Plant extracts and fractions exhibited high scavenging capacity against known radicals, enhanced superoxide dismutase and catalase activitiesand restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro enzymatic inhibition data, through inhibition of amylase and glucosidase activities. Administration of Pistacia lentiscus extracts significantly decreased carrageenan-induced mice paw oedema and reduced effectively IL-1β levels in cell culture, whereas Fraxinus angustifolia extracts showed good healing capacity against wounds when applied topically on rabbits. Pistacia lentiscus and Fraxinus angustifolia extracts showed good neuro-protection and restored cognitive functions in mice, while Clematis flammula extracts showed potent anti-ulcerogenic activity associated to a promising anti-mutagenic/genotoxic activity. HPLC-MS and NMR analyses allowed the identification and structural elucidation of several known and new anthocyanins, flavonols and flavanols. Therefore, Pistacia lentiscus, Fraxinus angustifolia and Clematis flammulacould be used in palliative treatments against inflammatory conditions and diabetes complications, as well as against deterioration of cognitive functions.

Keywords: pistacia lentiscus, clematis flammula, fraxinus angustifolia, phenolic compounds, biological activity

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