Search results for: role perceptions
8329 Targeting the EphA2 Receptor Tyrosine Kinases in Melanoma Cancer, both in Humans and Dogs
Authors: Shabnam Abdi, Behzad Toosi
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Background: Melanoma is the most lethal type of malignant skin cancer in humans and dogs since it spreads rapidly throughout the body. Despite significant advances in treatment, cancer at an advanced stage has a poor prognosis. Hence, more effective treatments are needed to enhance outcomes with fewer side effects. Erythropoietin-producing hepatocellular receptors are the largest family of receptor tyrosine kinases and are divided into two subfamilies, EphA and EphB, both of which play a significant role in disease, especially cancer. Due to their association with proliferation and invasion in many aggressive types of cancer, Eph receptor tyrosine kinases (Eph RTKs) are promising cancer therapy molecules. Because these receptors have not been studied in canine melanoma, we investigated how EphA2 influences survival and tumorigenicity of melanoma cells. Methods: Expression of EphA2 protein in canine melanoma cell lines and human melanoma cell line was evaluated by Western blot. Melanoma cells were transduced with lentiviral particles encoding Eph-targeting shRNAs or non-silencing shRNAs (control) for silencing the expression of EphA2 receptor, and silencing was confirmed by Western blotting and immunofluorescence. The effect of siRNA treatment on cellular proliferation, colony formation, tumorsphere assay, invasion was analyzed by Resazurin assay Matrigel invasion assay, respectively. Results: Expression of EphA2 was detected in canine and human melanoma cell lines. Moreover, stably silencing EphA2 by specific shRNAs significantly and consistently decreased the expression of EphA2 protein in both human and canine melanoma cells. Proliferation, colony formation, tumorsphere and invasion of melanoma cells were significantly decreased in EphA2 siRNA-treated cells compared to control. Conclusion: Our data provide the first functional evidence that the EphA2 receptor plays a critical role in the malignant cellular behavior of melanoma in both human and dogs.Keywords: ephA2, targeting, melanoma, human, canine
Procedia PDF Downloads 608328 Esophageal Premalignant and Malignant Epithelial Lesions: Pathological Characteristics and Value of Cyclooxygenase-2 Expression.
Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani
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Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.
Procedia PDF Downloads 3508327 Beneficial Effects of Curcumin against Stress Oxidative and Mitochondrial Dysfunction Induced by Trinitrobenzene Sulphonic Acid in Colon
Authors: Souad Mouzaoui, Bahia Djerdjouri
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Oxidative stress is one of the main factors involved in the onset and chronicity of inflammatory bowel disease (IBD). In this study, we investigated the beneficial effects of a potent natural antioxidant, curcumin (Cur) on colitis and mitochondrial dysfunction in trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Rectal instillation of the chemical irritant TNBS (30 mg kg-1) induced the disruption of distal colonic architecture and a massive inflammatory cells influx to the mucosa and submucosa layers. Under these conditions, daily administration of Cur (25 mg kg-1) efficiently decreased colitis scores in the inflamed distal colon by reducing leukocyte infiltrate as attested by reduced myeloperoxidase (MPO) activity. Moreover, the levels of nitrite, an end product of inducible NO synthase activity (iNOS) and malonyl dialdehyde (MDA), a marker of lipid peroxidation increased in a time depending manner in response to TNBS challenge. Conversely, the markers of the antioxidant pool, reduced glutathione (GSH) and catalase activity (CAT) were drastically reduced. Cur attenuated oxidative stress markers and partially restored CAT and GSH levels. Moreover, our results expanded the effect of Cur on TNBS-induced colonic mitochondrial dysfunction. In fact, TNBS induced mitochondrial swelling and lipids peroxidation. These events reflected in the opening of mitochondrial transition pore and could be an initial indication in the cascade process leading to cell death. TNBS inhibited also mitochondrial respiratory activity, caused overproduction of mitochondrial superoxide anion (O2-.) and reduced level of mitochondrial GSH. Nevertheless, Cur reduced the extent of mitochondrial oxidative stress induced by TNBS and restored colonic mitochondrial function. In conclusion, our results showed the critical role of oxidative stress in TNBS-induced colitis. They highlight the role of colonic mitochondrial dysfunction induced by TNBS, as a potential source of oxidative damages. Due to its potent antioxidant properties, Cur opens a promising therapeutic approach against oxidative inflammation in IBD.Keywords: colitis, curcumin, mitochondria, oxidative stress, TNBS
Procedia PDF Downloads 2538326 Exploring the History of Chinese Music Acoustic Technology through Data Fluctuations
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The study of extant musical sites can provide a side-by-side picture of historical ethnomusicological information. In their data collection on Chinese opera houses, researchers found that one Ming Dynasty opera house reached a width of nearly 18 meters, while all opera houses of the same period and after it was far from such a width, being significantly smaller than 18 meters. The historical transient fluctuations in the data dimension of width that caused Chinese theatres to fluctuate in the absence of construction scale constraints have piqued the interest of researchers as to why there is data variation in width. What factors have contributed to the lack of further expansion in the width of theatres? To address this question, this study used a comparative approach to conduct a venue experiment between this theater stage and another theater stage for non-heritage opera performances, collecting the subjective perceptions of performers and audiences at different theater stages, as well as combining BK Connect platform software to measure data such as echo and delay. From the subjective and objective results, it is inferred that the Chinese ancients discovered and understood the acoustical phenomenon of the Haas effect by exploring the effect of stage width on musical performance and appreciation of listening states during the Ming Dynasty and utilized this discovery to serve music in subsequent stage construction. This discovery marked a node of evolution in Chinese architectural acoustics technology driven by musical demands. It is also instructive to note that, in contrast to many of the world's "unsuccessful civilizations," China can use a combination of heritage and intangible cultural research to chart a clear, demand-driven course for the evolution of human music technology, and that the findings of such research will complete the course of human exploration of music acoustics. The findings of such research will complete the journey of human exploration of music acoustics, and this practical experience can be applied to the exploration and understanding of other musical heritage base data.Keywords: Haas effect, musical acoustics, history of acoustical technology, Chinese opera stage, structure
Procedia PDF Downloads 1848325 Opinions and Perceptions of Clinical Staff towards Caring for Obese Patients: A Qualitative Research Study in a Cardiac Centre in Bahrain
Authors: Catherine Mary Abou-Zaid, Sandra Goodwin
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This study was conducted in a cardiac center in Bahrain. The rise in the amount of obese patients’ both men and women, being admitted for surgical procedures has become an issue to the nurses and doctors as these patients pose a high risk of major complications arising from their problem. The cessation of obesity in the country is very high and obesity-related diseases has been the cause of concern among men and women, also related individual diseases such as cardiovascular, diabetes and chronic respiratory diseases are rising dramatically within Bahrain in the last 10 years. Rationale for the Study: The ontological approach will help to understand and assess the true nature of the social world and how the world looks at obesity. Obesity has to be looked at as being a realistic ongoing issue. The epistemological approach will look at the theory of the origins of the nature of knowledge, set the rule of validating and learning in the social world of what can be done to curb this concept and how this can help prevent otherwise preventable diseases. Design Methodology: The qualitative design methodology took the form of an ontological/epistemological approach using phenomenology as a framework. The study was based on a social research issue, therefore, ontological ‘realism and idealism’ will feature as the nature of the world from a social and natural context. Epistemological positions of the study will be how we as researchers will find the actual social world and the limiting of that knowledge. The one-to-one interviews will be transcribed and the taped verbatim will be coded and charted giving the thematic analytic results. Recommendations: The significance of the research brought many recommendations. These recommendations were taken from the themes and sub-themes and were presented to the centers management and the necessary arrangements for updating knowledge and attitudes towards obesity in cardiac patients was then presented to the in-service education department. Workshops and training sessions on promoting health education were organized and put into the educational calendar for the next academic year. These sessions would look at patient autonomy, the patients’ rights, healthy eating for patients and families and the risks associated with obesity in cardiac disease processes.Keywords: cardiac patients, diabetes, education & training, obesity cessation, qualitative
Procedia PDF Downloads 3328324 Responsibility of International Financial Institutions for Harmful Environmental Consequences Arising from Their Development Interventions
Authors: Reham Barakat
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Over the last few decades, the influence of International Financial Institutions (IFIs), especially the World Bank (WB), has significantly increased. Since the early 1980s, IFIs have assumed greater role, especially in developing countries; their total lending has dramatically increased, affecting billions of people in their Borrower States. Though the purpose of the development assistance provided by IFIs is to alleviate poverty and promote economic and social development in their member countries, IFIs have been subject to massive criticism by civil society institutions, international NGOs and local communities for the harmful environmental, social and economic impacts resulting from their development interventions in borrower countries, such as deforestation, displacement of indigenous peoples, and unemployment. While the role of IFIs has expanded over time, affecting billions of people, their accountability mechanisms remained behind and were criticized for lacking sufficient independency and enforceability. The serious adverse environmental impacts of the World Bank’s funded projects, along with their weak accountability mechanisms, raises the question of 'To what extent IFIs should be held internationally responsible for the harmful environmental consequences arising from their development interventions?'. This paper argues that IFIs are legally responsible for the harmful environmental consequences arising from their development interventions. The study (i) identifies the applicable laws and relevant primary rules from which the international environmental obligations of IFIs towards their borrower countries are derived (ii) assesses the World Bank’s compliance to the principles of the International Environmental Law including the precautionary principle, the polluter pays principle, and the principle of Good-Neighborliness, (iii) assesses the World Bank’s current internal accountability mechanisms for harmful environmental impacts resulting from the World Bank’s funded projects, and finally (iv) identifies the appropriate dispute settlement mechanisms to which states and non-state actors could raise their claims against IFIs for harmful environmental consequences arising from their interventions.Keywords: international environmental law, international financial institutions, international responsibility, world bank, environmental and social safeguards
Procedia PDF Downloads 1708323 OAS and Interstate Dispute Resolution at the Beginning of the 21st Century: General Pattern and Peculiarities
Authors: Victor Jeifets, Liliia Khadorich
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The paper describes the OAS role in dispute resolution. The authors make an attempt to identify a general pattern of the OAS activities within the peaceful settlement of interstate conflicts, in the beginning of 21st century, as well as to analyze some features of Honduras–Belize, Nicaragua–Honduras, Honduras–El Salvador, Costa-Rica–Nicaragua, Colombia–Ecuador cases.Keywords: OAS, peace maintenance, border dispute, dispute resolution, peaceful settlement
Procedia PDF Downloads 4928322 A Regional Innovation System Model Based on the Systems Thinking Approach
Authors: Samara E., Kilintzis P., Katsoras E., Martinidis G.
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Regions play an important role in the global economy by driving research and innovation policies through a major tool, the Regional Innovation System (RIS). RIS is a social system that encompasses the systematic interaction of the various organizations that comprise it in order to improve local knowledge and innovation. This article describes the methodological framework for developing and validating a RIS model utilizing system dynamics. This model focuses on the functional structure of the RIS, separating it in six diverse, interacting sub-systems.Keywords: innovations, regional development, systems thinking, social system
Procedia PDF Downloads 738321 Loss of Function of Only One of Two CPR5 Paralogs Causes Resistance Against Rice Yellow Mottle Virus
Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar
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Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus
Procedia PDF Downloads 1188320 Bridging Binaries: Exploring Students' Conceptions of Good Teaching within Teacher-Centered and Learner-Centered Pedagogies of Their Teachers in Disadvantaged Public Schools in the Philippines
Authors: Julie Lucille H. Del Valle
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To improve its public school education, the Philippines took a radical curriculum reform in 2012, by launching the K-to-12 program which not only added two years to its basic education but also mandated for a replacement of traditional teaching with learner-centered pedagogy, an instruction whose western underpinnings suggest improving student achievement, thus, making pedagogies in the country more or less similar with those in Europe and USA. This policy, however, placed learner-centered pedagogy in a binary opposition against teacher-centered instruction, creating a simplistic dichotomy between good and bad teaching. It is in this dichotomy that this study seeks to explore, using Critical Pedagogy of the Place as the lens, in understanding what constitutes good teaching across a range of learner-centered and teacher-centered pedagogies in the context of public schools in disadvantaged communities. Furthermore, this paper examines how pedagogical homogeneity, arguably influenced by dominant global imperatives with economic agenda – often referred as economisation of education – not only thins out local identities as structures of global schooling become increasingly similar but also limits the concept of good teaching to student outcomes and corporate employability. This paper draws from qualitative research on students, thus addressing the gap created by studies on good teaching which looked mainly into the perceptions of teachers and administrators, while overlooking those of students whose voices must be considered in the formulation of inclusive policies that advocate for true education reform. Using ethnographic methods including student focus groups, classroom observations, and teacher interviews, responses from students of disadvantaged schools reveal that good teaching includes both learner-centered and teacher-centered practices that incorporate ‘academic caring’ which sustains their motivation to achieve in school despite the challenging learning environments. The combination of these two pedagogies equips students with life-long skills necessary to gain equal access to sustainable economic opportunities in their local communities.Keywords: critical pedagogy of the place, good teaching, learner-centered pedagogy, placed-based instruction
Procedia PDF Downloads 2618319 Usage of Internet Technology in Financial Education and Financial Inclusion by Students of Economics Universities
Authors: B. Frączek
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The paper analyses the usage of the Internet by university students in Visegrad Countries (4V Countries) who study economic fields in their formal and informal financial education and captures the areas of untapped potential of Internet in educational processes. Higher education and training, technological readiness, and the financial market development are in the group of pillars, that are key for efficiency driven economies. These three pillars have become an inspiration to the research on using the Internet in the financial education among economic university students as the group of the best educated people in finance. The financial education is a process that allows for improving the level of financial literacy. In turn, the financial literacy it is the set of financial knowledge, skills, awareness and patterns influencing the financial decisions. The level of financial literacy influences the level of financial well-being of individuals, determines the scale of saving of households and at the same time gives the greater chance for sustainable and more predictable development of the financial market with the positive impact on economy. The financial literacy is necessary for each group of society but its appropriate level is desirable especially in respect of economics students as future participants of financial markets as well as the experts and advisors in financial decision making. The low level of financial literacy is the great problem of many target groups in both developing and developed countries and the financial education is seen as the best way of improving this situation. Also the financial inclusion plays the special role in enhancing the level of financial literacy in the aspect of education by practice as well as due to interrelation between level of financial literacy and degree of financial inclusion. Despite many initiatives under financial education, the level of financial literacy is still very low. Scientists still search for new ways of solving this problem. One of the proposal is more effective usage of the new technology in financial education, especially the Internet, because of the growing popularity of e-learning and the increasing number of Internet users, especially among young people who are called the Generation Net. Due to special role of the university students studying the economics fields for the future financial markets, students of four universities from Visegrad Countries (Czech Republic, Hungary, Poland and Slovakia) were invited to participate in the survey. The aim of the article is to present the level and ways of using the Internet technology in financial education and indicating the so far unused or underused opportunities.Keywords: financial education, financial inclusion, financial literacy, internet and university education
Procedia PDF Downloads 3148318 Hepatocyte-Intrinsic NF-κB Signaling Is Essential to Control a Systemic Viral Infection
Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder
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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance
Procedia PDF Downloads 1918317 Chebyshev Polynomials Relad with Fibonacci and Lucas Polynomials
Authors: Vandana N. Purav
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Fibonacci and Lucas polynomials are special cases of Chebyshev polynomial. There are two types of Chebyshev polynomials, a Chebyshev polynomial of first kind and a Chebyshev polynomial of second kind. Chebyshev polynomial of second kind can be derived from the Chebyshev polynomial of first kind. Chebyshev polynomial is a polynomial of degree n and satisfies a second order homogenous differential equation. We consider the difference equations which are related with Chebyshev, Fibonacci and Lucas polynomias. Thus Chebyshev polynomial of second kind play an important role in finding the recurrence relations with Fibonacci and Lucas polynomials. Procedia PDF Downloads 3688316 The Mediating Role of Social Connectivity in the Effect of Positive Personality and Alexithymia on Life Satisfaction: Analysis Based on Structural Equation Model
Authors: Yulin Zhang, Kaixi Dong, Guozhen Zhao
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Background: Different levels of life satisfaction are associated with some individual differences. Understanding the mechanism between them will help to enhance an individual’s well-being. On the one hand, traditional personality such as extraversion has been considered as the most stable and effective factor in predicting life satisfaction to the author’s best knowledge. On the other, individual emotional difference, such as alexithymia (difficulties identifying and describing one’s own feelings), is also closely related to life satisfaction. With the development of positive psychology, positive personalities such as virtues attract wide attention. And according to the broaden-and-build theory, social connectivity may mediate between emotion and life satisfaction. Therefore, the current study aims to explore the mediating role of social connectivity in the effect of positive personality and alexithymia on life satisfaction. Method: This study was conducted with 318 healthy Chinese college students whose age range from 18 to 30. Positive personality (including interpersonal, vitality, and cautiousness) was measured by the Chinese version of Values in Action Inventory of Strengths (VIA-IS). Alexithymia was measured by the Toronto Alexithymia Scale (TAS), and life satisfaction was measured by Satisfaction With Life Scale (SWLS). And social connectivity was measured by six items which have been used in previous studies. Each scale showed high reliability and validity. The mediating model was examined in Mplus 7.2 within a structural equation modeling (SEM) framework. Findings: The model fitted well and results revealed that both positive personality (95% confidence interval of indirect effect was [0.023, 0.097]) and alexithymia (95% confidence interval of indirect effect was [-0.270, -0.089]) predicted life satisfaction level significantly through social connectivity. Also, only positive personality significantly and directly predicted life satisfaction compared to alexithymia (95% confidence interval of direct effect was [0.109, 0.260]). Conclusion: Alexithymia predicts life satisfaction only through social connectivity, which emphasizes the importance of social bonding in enhancing the well-being of Chinese college students with alexithymia. And the positive personality can predict life satisfaction directly or through social connectivity, which provides implications for enhancing the well-being of Chinese college students by cultivating their virtue and positive psychological quality.Keywords: alexithymia, life satisfaction, positive personality, social connectivity
Procedia PDF Downloads 1678315 An Advanced Method of Minimizing Unforeseen Disruptions within a Manufacturing System: A Case Study of Amico, South Africa
Authors: Max Moleke
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Manufacturing industries are faced with different types of problems. One of the most important role of controlling and monitoring a production process is to actually determine how to deal with unforeseen disruption when they arise. A majority of manufacturing tern to spend huge amount of money in order to meet up with their customers requirements and demand but due to instabilities within the manufacturing process, this objectives and goals are difficult to be achieved. In this research, we have developed a feedback control system that can minimize instability within the manufacturing system in order to boost the system output and productivity.Keywords: disruption, scheduling, manufacturing, instability
Procedia PDF Downloads 3288314 Towards a Critical Disentanglement of the ‘Religion’ Nexus in the Global East
Authors: Daan F. Oostveen
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‘Religion’ as a term is not native to the Global East. The concept ‘religion’ is both understood in its meaning of ‘religious traditions’, commonly referring to the ‘World Religions’ and in its adjective meaning ‘the religious’ or ‘religiosity’ as a separate domain of human culture, commonly contrasted to the secular. Though neither of these understandings are native to the historical worldviews of East Asia, their development in modern Western scholarship has had an enormous impact on the self-understanding of cultural diversity in the Global East as well. One example is the identification and therefore elevation to the status of World Religion of ‘Buddhism’ which connected formerly dispersed religious practices throughout the Global East and subsumed them under this powerful label. On the other hand, we see how popular religiosity, shamanism and hybrid cultural expressions have become excluded from genuine religion; this had an immense impact on the sense of legitimacy of these practices, which became sometimes labeled as superstition are rejected as magic. Our theoretical frameworks on religion in the Global East do not always consider the complex power dynamics between religious actors, both elites and lay expressions of religion in everyday life, governments and religious studies scholars. In order to get a clear image of how religiosity functions in the context of the Global East, we have to take into account these power dynamics. What is important in particular is the issue of religious identity or absence of religious identity. The self-understanding of religious actors in the Global East is often very different from what scholars of religion observe. Religious practice, from an etic perspective, is often unrelated to religious identification from an emic perspective. But we also witness the rise of Christian churches in the Global East, in which religious identity and belonging does play a pivotal role. Finally, religion in the Global East has since the beginning of the 20th Century been conceptualized as the ‘other’ or republicanism or Marxist-Maoist ideology. It is important not to deny the key role of colonial thinking in the process of religion formation in the Global East. In this paper, it is argued that religious realities constituted emerging as a result from our theory of religion, and that these religious realities in turn inform our theory. Therefore, the relationship between phenomenology of religion and theory of religion can never be disentangled. In fact, we have to acknowledge that our conceptualizations of religious diversity are always already influenced by our valuation of those cultural expressions that we have come to call ‘religious’.Keywords: global east, religion, religious belonging, secularity
Procedia PDF Downloads 1368313 The Gender Digital Divide in Education: The Case of Students from Rural Area from Republic of Moldova
Authors: Bărbuță Alina
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The inter-causal relationship between social inequalities and the digital divide raises the relation issue of gender and information and communication technologies (ICT) - a key element in achieving sustainable development. In preparing generations as future digital citizens and for active socio-economic participation, ICT plays a key role in respecting gender equality. Although several studies over the years have shown that gender plays an important role in digital exclusion, in recent years, many studies with a focus on economically developed or developing countries identify an improvement in these aspects and a gap narrowing. By measuring students' digital competencies level, this paper aims to identify and analyse the existing gender digital inequalities among students. Our analyses are based on a sample of 1526 middle school students residing in rural areas from Republic of Moldova (54.2% girls, mean age 14,00, SD = 1.02). During the online survey they filled in a questionnaire adapted from the (yDSI) ”The Youth Digital Skills Indicator”. The instrument measures the level of five digital competence areas indicated in The European Digital Competence Framework (DigiCom 2.3.). Our results, based on t-test, indicate that depending on gender, there are no statistically significant differences regarding the levels of digital skills in 3 areas: Information navigation and processing; Communication and interaction; Problem solving. However, were identified significant differences in the level of digital skills in the area of ”Digital content creation” [t(1425) = 4.20, p = .000] and ”Safety” [t(1421) = 2.49, p = .000], with higher scores recorded by girls. Our results contradicts the general stereotype regarding the low level of digital competence among girls, in our sample girls scores being on pear with boys and even bigger in knowledge related to digital content creation and online safety skills. Additional investigations related to boys competence on digital safety are necessary as the implication of their low scores on this dimension may suggest boys exposure to digital threats.Keywords: digital divide, education, gender digital divide, digital literacy, remote learning
Procedia PDF Downloads 1018312 Examining the Role of Corporate Culture in Driving Firm Performance
Authors: Lovorka Galetić, Ivana Načinović Braje, Nevenka Čavlek
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The purpose of this paper is to analyze the relationship between corporate culture and firm performance. Extensive theoretical and empirical evidence on this issue is provided. A quantitative methodology was used to explore relationship between corporate culture and performance among large Croatian companies. Corporate culture was explored by using Denison framework. The research revealed a positive, statistically significant relationship between mission and performance. Other dimensions of corporate culture (involvement, consistency and adaptability) show only partial relationship with performance.Keywords: corporate culture, Croatia, Denison culture model, performance
Procedia PDF Downloads 5288311 The Key Role of a Bystander Improving the Effectiveness of Cardiopulmonary Resuscitation Performed in Extra-Urban Areas
Authors: Leszek Szpakowski, Daniel Celiński, Sławomir Pilip, Grzegorz Michalak
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The aim of the study was to analyse the usefulness of the 'E-rescuer' pilot project planned to be implemented in a chosen area of Eastern Poland in the cases of suspected sudden cardiac arrests in the extra-urban areas. Inventing an application allowing to dispatch simultaneously both Medical Emergency Teams and the E-rescuer to the place of the accident is the crucial assumption of the mentioned pilot project. The E-rescuer is defined to be the trained person able to take effective basic life support and to use automated external defibrillator. Having logged in using a smartphone, the E-rescuer's readiness is reported online to provide cardiopulmonary resuscitation exactly at the given location. Due to the accurately defined location of the E-rescuer, his arrival time is possible to be precisely fixed, and the substantive support through the displayed algorithms is capable of being provided as well. Having analysed the medical records in the years 2015-2016, cardiopulmonary resuscitation was considered to be effective when an early indication of circulation was provided, and the patient was taken to hospital. In the mentioned term, there were 2.291 cases of a sudden cardiac arrest. Cardiopulmonary resuscitation was taken in 621 patients in total including 205 people in the urban area and 416 in the extra-urban areas. The effectiveness of cardiopulmonary resuscitation in the extra-urban areas was much lower (33,8%) than in the urban (50,7%). The average ambulance arrival time was respectively longer in the extra-urban areas, and it was 12,3 minutes while in the urban area 3,3 minutes. There was no significant difference in the average age of studied patients - 62,5 and 64,8 years old. However, the average ambulance arrival time was 7,6 minutes for effective resuscitations and 10,5 minutes for ineffective ones. Hence, the ambulance arrival time is a crucial factor influencing on the effectiveness of cardiopulmonary resuscitation, especially in the extra-urban areas where it is much longer than in the urban. The key role of trained E-rescuers being nearby taking basic life support before the ambulance arrival can effectively support Emergency Medical Services System in Poland.Keywords: basic life support, bystander, effectiveness, resuscitation
Procedia PDF Downloads 2038310 Focus Group Study Exploring Researchers Perspective on Open Science Policy
Authors: E. T. Svahn
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Knowledge about the factors that influence the exchange between research and society is of the utmost importance for developing collaboration between different actors, especially in future science policy development and the creation of support structures for researchers. Among other things, how researchers look at the surrounding open science policy environment and what conditions and attitudes they have for interacting with it. This paper examines the Finnish researchers' attitudes towards open science policies in 2020. Open science is an integrated part of researchers' daily lives and supports not only the effectiveness of research outputs but also the quality of research. Open science policy in ideal situation is seen as a supporting structure that enables the exchange between research and society, but in other situation, it can end up being red tape generating obstacles and hindering possibilities of making science in an efficient way. Results of this study were carried out through focus group interviews. This qualitative research method was selected because it aims to understand the phenomenon under study. In addition, focus group interviews produce diverse and rich material that would not be available with other research methods. Focus group interviews have well-established applications in social science, especially in understanding the perspectives and experiences of research subjects. In this study, focus groups were used in studying the mindset and actions of researchers. Each group's size was between 4-10 people, and the aim was to bring out different perspectives on the subject. The interviewer enabled the presentation of different perceptions and opinions, and the focus group interviews were recorded and written as text. The material was analysed using grounded theory method. The results are presented as thematic areas, theoretical model, and as direct quotations. Attitudes towards open science policy can vary greatly depending on the research area. This study shows that the open science policy demands in medicine, technology, and natural sciences compared to social sciences, educational sciences, and the humanities, varies somewhat. The variation in attitudes between different research areas can thus be largely explained by the fact that the research output and ethical code vary significantly between certain subjects. This study aims to increase understanding of the nuances to what extent open science policies should be tailored for different disciplines and research areas.Keywords: focus group interview, grounded theory, open science policy, science policy
Procedia PDF Downloads 1558309 Metaphysical and Mystical Viewpoints of Roozbihan Baqli Shirazi on the Quran
Authors: Seyed Abdol Majid Hosseinizadeh
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This study aims at an assessment of the part of interpretational issues on the Quran in Roozbihan Baqli Shirazi's books, who has been a mystic and Sufi in the 12th century. He has written many mystical books which Henry Corbin and others have introduced and researched, especially his commentary on the Quran called Ara'is al-Bayan, but he also has other interpretational viewpoints on the Quran spread throughout his mystical works, which have not been considered. In this paper, it has been shown through a documentary method that Quranic verses and their interpretations also have a great role in his other works.Keywords: interpretation, Islamic mysticism, Quran, Roozbihan Baqli Shirazi
Procedia PDF Downloads 2568308 Fire Resilient Cities: The Impact of Fire Regulations, Technological and Community Resilience
Authors: Fanny Guay
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Building resilience, sustainable buildings, urbanization, climate change, resilient cities, are just a few examples of where the focus of research has been in the last few years. It is obvious that there is a need to rethink how we are building our cities and how we are renovating our existing buildings. However, the question remaining is how can we assure that we are building sustainable yet resilient cities? There are many aspects one can touch upon when discussing resilience in cities, but after the event of Grenfell in June 2017, it has become clear that fire resilience must be a priority. We define resilience as a holistic approach including communities, society and systems, focusing not only on resisting the effects of a disaster, but also how it will cope and recover from it. Cities are an example of such a system, where components such as buildings have an important role to play. A building on fire will have an impact on the community, the economy, the environment, and so the entire system. Therefore, we believe that fire and resilience go hand in hand when we discuss building resilient cities. This article aims at discussing the current state of the concept of fire resilience and suggests actions to support the built of more fire resilient buildings. Using the case of Grenfell and the fire safety regulations in the UK, we will briefly compare the fire regulations in other European countries, more precisely France, Germany and Denmark, to underline the difference and make some suggestions to increase fire resilience via regulation. For this research, we will also include other types of resilience such as technological resilience, discussing the structure of buildings itself, as well as community resilience, considering the role of communities in building resilience. Our findings demonstrate that to increase fire resilience, amending existing regulations might be necessary, for example, how we performed reaction to fire tests and how we classify building products. However, as we are looking at national regulations, we are only able to make general suggestions for improvement. Another finding of this research is that the capacity of the community to recover and adapt after a fire is also an essential factor. Fundamentally, fire resilience, technological resilience and community resilience are closely connected. Building resilient cities is not only about sustainable buildings or energy efficiency; it is about assuring that all the aspects of resilience are included when building or renovating buildings. We must ask ourselves questions as: Who are the users of this building? Where is the building located? What are the components of the building, how was it designed and which construction products have been used? If we want to have resilient cities, we must answer these basic questions and assure that basic factors such as fire resilience are included in our assessment.Keywords: buildings, cities, fire, resilience
Procedia PDF Downloads 1708307 New Insights for Soft Skills Development in Vietnamese Business Schools: Defining Essential Soft Skills for Maximizing Graduates’ Career Success
Authors: Hang T. T. Truong, Ronald S. Laura, Kylie Shaw
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Within Vietnam's system of higher education, its schools of business play a vital role in supporting the country’s economic objectives. However, the crucial contribution of soft skills for maximal success within the business sector has to date not been adequately recognized by its business schools. This being so, the development of the business school curriculum in Vietnam has not been able to 'catch up', so to say, with the burgeoning need of students for a comprehensive soft skills program designed to meet the national and global business objectives of their potential employers. The burden of the present paper is first to reveal the results of our survey in Vietnam which make explicit the extent to which major Vietnamese industrial employers’ value the potential role that soft skill competencies can play in maximizing business success. Our final task will be to determine which soft skills employers discern as best serving to maximize the economic interests of Vietnam within the global marketplace. Semi-structured telephone interviews have been conducted with the 15 representative Head Employers of Vietnam's reputedly largest and most successful of the diverse business enterprises across Vietnam. The findings of the study indicate that all respondents highly value the increasing importance of soft skills in business success. Our critical analysis of respondent data reveals that 19 essential soft skills are deemed by employers as integral to business workplace efficacy and should thus be integrated into the formal business curriculum. We are confident that our study represents the first comprehensive and specific survey yet undertaken within the business sector in Vietnam which accesses and analyses the opinions of representative employers from major companies across the country in regard to the growing importance of 19 specific soft skills essential for maximizing overall business success. Our research findings also reveal that the integration into business school curriculums nationwide of the soft skills we have identified is of paramount importance to advance the national and global economic interests of Vietnam.Keywords: business curriculum, business graduates, employers’ perception, soft skills
Procedia PDF Downloads 3208306 Role of von Willebrand Factor Antigen as Non-Invasive Biomarker for the Prediction of Portal Hypertensive Gastropathy in Patients with Liver Cirrhosis
Authors: Mohamed El Horri, Amine Mouden, Reda Messaoudi, Mohamed Chekkal, Driss Benlaldj, Malika Baghdadi, Lahcene Benmahdi, Fatima Seghier
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Background/aim: Recently, the Von Willebrand factor antigen (vWF-Ag)has been identified as a new marker of portal hypertension (PH) and its complications. Few studies talked about its role in the prediction of esophageal varices. VWF-Ag is considered a non-invasive approach, In order to avoid the endoscopic burden, cost, drawbacks, unpleasant and repeated examinations to the patients. In our study, we aimed to evaluate the ability of this marker in the prediction of another complication of portal hypertension, which is portal hypertensive gastropathy (PHG), the one that is diagnosed also by endoscopic tools. Patients and methods: It is about a prospective study, which include 124 cirrhotic patients with no history of bleeding who underwent screening endoscopy for PH-related complications like esophageal varices (EVs) and PHG. Routine biological tests were performed as well as the VWF-Ag testing by both ELFA and Immunoturbidimetric techniques. The diagnostic performance of our marker was assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and receiver operating characteristic curves. Results: 124 patients were enrolled in this study, with a mean age of 58 years [CI: 55 – 60 years] and a sex ratio of 1.17. Viral etiologies were found in 50% of patients. Screening endoscopy revealed the presence of PHG in 20.2% of cases, while for EVsthey were found in 83.1% of cases. VWF-Ag levels, were significantly increased in patients with PHG compared to those who have not: 441% [CI: 375 – 506], versus 279% [CI: 253 – 304], respectively (p <0.0001). Using the area under the receiver operating characteristic curve (AUC), vWF-Ag was a good predictor for the presence of PHG. With a value higher than 320% and an AUC of 0.824, VWF-Ag had an 84% sensitivity, 74% specificity, 44.7% positive predictive value, 94.8% negative predictive value, and 75.8% diagnostic accuracy. Conclusion: VWF-Ag is a good non-invasive low coast marker for excluding the presence of PHG in patients with liver cirrhosis. Using this marker as part of a selective screening strategy might reduce the need for endoscopic screening and the coast of the management of these kinds of patients.Keywords: von willebrand factor, portal hypertensive gastropathy, prediction, liver cirrhosis
Procedia PDF Downloads 2058305 The Interplay between Consumer Knowledge, Cognitive Effort, Financial Healthiness and Trust in the Financial Marketplace
Authors: Torben Hansen
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While trust has long been regarded as one of the most critical variables for developing and maintaining well-functioning financial customer-seller relationships it can be suggested that trust not only relates to customer trust in individual companies (narrow-scope trust). Trust also relates to the broader business context in which consumers may carry out their financial behaviour (broad-scope trust). However, despite the well-recognized significance of trust in marketing research, only few studies have investigated the role of broad-scope trust in consumer financial behaviour. Moreover, as one of its many serious outcomes, the global financial crisis has elevated the need for an improved understanding of the role of broad-scope trust in consumer financial services markets. Only a minority of US and European consumers are currently confident in financial companies and ‘financial stability’ and ‘trust’ are now among the top reasons for choosing a bank. This research seeks to address this shortcoming in the marketing literature by investigating direct and moderating effects of broad-scope trust on consumer financial behaviour. Specifically, we take an ability-effort approach to consumer financial behaviour. The ability-effort approach holds the basic premise that the quality of consumer actions is influenced by ability factors, for example consumer knowledge and cognitive effort. Our study is based on two surveys. Survey 1 comprises 1,155 bank consumers, whereas survey 2 comprises 764 pension consumers. The results indicate that broad-scope trust negatively moderates relationships between knowledge and financial healthiness and between cognitive effort and financial healthiness. In addition, it is demonstrated that broad-scope trust negatively influences cognitive effort. Specifically, the results suggest that broad-scope trust contributes to the financial well-being of consumers with limited financial knowledge and processing capabilities. Since financial companies are dependent on customers to pay their loans and bills they have a greater interest in developing relations with consumers with a healthy financial behaviour than with the opposite. Hence, financial managers should be engaged with monitoring and influencing broad-scope trust. To conclude, by taking into account the contextual effect of broad-scope trust, the present study adds to our understanding of knowledge-effort-behaviour relationship in consumer financial markets.Keywords: cognitive effort, customer-seller relationships, financial healthiness, knowledge, trust
Procedia PDF Downloads 4418304 Embodied Cognition as a Concept of Educational Neuroscience and Phenomenology
Authors: Elham Shirvani-Ghadikolaei
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In this paper, we examine the connection between the human mind and body within the framework of Merleau-Ponty's phenomenology. We study the role of this connection in designing more efficient learning environments, alongside the findings in physical recognition and educational neuroscience. Our research shows the interplay between the mind and the body in the external world and discusses its implications. Based on these observations, we make suggestions as to how the educational system can benefit from taking into account the interaction between the mind and the body in educational affairs.Keywords: educational neurosciences, embodied cognition, pedagogical neurosciences, phenomenology
Procedia PDF Downloads 3168303 Effects of Kolavironon Liver Oxidative Stress and Beta-Cell Damage in Streptozotocin-Induced Diabetic Rats
Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju
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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis
Procedia PDF Downloads 3858302 Advancing Agriculture through Technology: An Abstract of Research Findings
Authors: Eugene Aninagyei-Bonsu
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Introduction: Agriculture has been a cornerstone of human civilization, ensuring food security and livelihoods for billions of people worldwide. In recent decades, rapid advancements in technology have revolutionized the agricultural sector, offering innovative solutions to enhance productivity, sustainability, and efficiency. This abstract summarizes key findings from a research study that explores the impacts of technology in modern agriculture and its implications for future food production systems. Methodologies: The research study employed a mixed-methods approach, combining quantitative data analysis with qualitative interviews and surveys to gain a comprehensive understanding of the role of technology in agriculture. Data was collected from various stakeholders, including farmers, agricultural technicians, and industry experts, to capture diverse perspectives on the adoption and utilization of agricultural technologies. The study also utilized case studies and literature reviews to contextualize the findings within the broader agricultural landscape. Major Findings: The research findings reveal that technology plays a pivotal role in transforming traditional farming practices and driving innovation in agriculture. Advanced technologies such as precision agriculture, drone technology, genetic engineering, and smart irrigation systems have significantly improved crop yields, reduced environmental impact, and optimized resource utilization. Farmers who have embraced these technologies have reported increased productivity, enhanced profitability, and improved resilience to environmental challenges. Furthermore, the study highlights the importance of accessible and affordable technology solutions for smallholder farmers in developing countries. Mobile applications, sensor technologies, and digital platforms have enabled small-scale farmers to access market information, weather forecasts, and agricultural best practices, empowering them to make informed decisions and improve their livelihoods. The research emphasizes the need for targeted policies and investments to bridge the digital divide and promote equitable technology adoption in agriculture. Conclusion: In conclusion, this research underscores the transformative potential of technology in agriculture and its critical role in advancing sustainable food production systems. The findings suggest that harnessing technology can address key challenges facing the agricultural sector, including climate change, resource scarcity, and food insecurity. By embracing innovation and leveraging technology, farmers can enhance their productivity, profitability, and resilience in a rapidly evolving global food system. Moving forward, policymakers, researchers, and industry stakeholders must collaborate to facilitate the adoption of appropriate technologies, support capacity building, and promote sustainable agricultural practices for a more resilient and food-secure future.Keywords: technology development in modern agriculture, the influence of information technology access in agriculture, analyzing agricultural technology development, analyzing of the frontier technology of agriculture loT
Procedia PDF Downloads 358301 Migrantional Entrepreneurship: Ethnography of a Journey That Changes Lives and the Territory
Authors: Francesca Alemanno
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As a complex socio-spatial phenomenon, migration is a practice that also contains a strong imaginative component with respect to the place that, through displacement, one person wants to reach. Every migrant has undertaken his journey having in his mind an image of the displacement he was about to make, of its implications and finally, of the place or city in which he was or would have liked to land. Often, however, the imaginary that has come to build before departure does not fully correspond to the reality of landing; this discrepancy, which can be more or less wide, plays an important role in the relationship that is established with the territory and in the evolution, therefore, of the city itself. In this sense, therefore, the clash that occurs between the imagined and the real is one of the factors that can contribute to making the entry of a migrant into new territory as critical as it can be. Starting from this perspective, the experiences of people who derive from a migratory context and who, over time, manage to create a bond with the land of reception, are taken into account as stories of resistance as they are necessarily charged with a force that is capable of driving difficult and articulated processes of change. The phenomenon of migrant entrepreneurship that is taken into consideration by this abstract plays a very important role because it highlights the story of many people who have managed to build such a close bond with the new territory of arrival that they can imagine and then realize the construction of their own personal business. The margin of contrast between the imagined city and the one that will be inhabited will be observed through the narratives of those who, through the realization of his business project has acted directly on the reality in which he landed. The margin of contrast that exists between the imagined city and the one actually inhabited, together with the implications that this may have on real life, has been observed and analyzed through a period of fieldwork, practicing ethnography, through the narratives of people who find themselves living in a new city as a result of a migration path, and has been contextualized with the support of semi-structured interviews and field notes. At the theoretical level, the research is inserted into a constructionist framework, particularly suited to detect and analyze processes of change, construction of the imaginary and its own modification, being able to capture the consequent repercussions of this process on the conceptual, emotional and practical level.Keywords: entrepreneurship, imagination, migration, resistance
Procedia PDF Downloads 1518300 Role of Autophagic Lysosome Reformation for Cell Viability in an in vitro Infection Model
Authors: Muhammad Awais Afzal, Lorena Tuchscherr De Hauschopp, Christian Hübner
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Introduction: Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway, which can be induced by extrinsic and intrinsic stressors in living systems to adapt to fluctuating environmental conditions. In the context of inflammatory stress, autophagy contributes to the elimination of invading pathogens, the regulation of innate and adaptive immune mechanisms, and regulation of inflammasome activity as well as tissue damage repair. Lysosomes can be recycled from autolysosomes by the process of autophagic lysosome reformation (ALR), which depends on the presence of several proteins including Spatacsin. Thus ALR contributes to the replenishment of lysosomes that are available for fusion with autophagosomes in situations of increased autophagic turnover, e.g., during bacterial infections, inflammatory stress or sepsis. Objectives: We aimed to assess whether ALR plays a role for cell survival in an in-vitro bacterial infection model. Methods: Mouse embryonic fibroblasts (MEFs) were isolated from wild-type mice and Spatacsin (Spg11-/-) knockout mice. Wild-type MEFs and Spg11-/- MEFs were infected with Staphylococcus aureus (multiplication of infection (MOI) used was 10). After 8 and 16 hours of infection, cell viability was assessed on BD flow cytometer through propidium iodide intake. Bacterial intake by cells was also calculated by plating cell lysates on blood agar plates. Results: in-vitro infection of MEFs with Staphylococcus aureus showed a marked decrease of cell viability in ALR deficient Spatacsin knockout (Spg11-/-) MEFs after 16 hours of infection as compared to wild-type MEFs (n=3 independent experiments; p < 0.0001) although no difference was observed for bacterial intake by both genotypes. Conclusion: Suggesting that ALR is important for the defense of invading pathogens e.g. S. aureus, we observed a marked increase of cell death in an in-vitro infection model in cells with compromised ALR.Keywords: autophagy, autophagic lysosome reformation, bacterial infections, Staphylococcus aureus
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