Search results for: toll plaza

Authors: Onur Kaya, Ilknur Tukenmez

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In this study, we consider vehicle routing problems on networks with alternative direct links between nodes, and we analyze a multi-objective problem considering the financial, environmental and social objectives in this context. In real life, there might exist several alternative direct roads between two nodes, and these roads might have differences in terms of their lengths and durations. For example, a road might be shorter than another but might require longer time due to traffic and speed limits. Similarly, some toll roads might be shorter or faster but require additional payment, leading to higher costs. We consider such alternative links in our problem and develop a mixed integer linear programming model that determines which alternative link to use between two nodes, in addition to determining the optimal routes for different vehicles, depending on the model objectives and constraints. We consider the minimum cost routing as the financial objective for the company, minimizing the CO2 emissions and gas usage as the environmental objectives, and optimizing the driver working conditions/working hours, and minimizing the risks of accidents as the social objectives. With these objective functions, we aim to determine which routes, and which alternative links should be used in addition to the speed choices on each link. We discuss the results of the developed vehicle routing models and compare their results depending on the system parameters.

Keywords: vehicle routing, alternative links between nodes, mixed integer linear programming, triple bottom line accounting

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Authors: Uche A. Nnawulezi

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Undoubtedly, despite all efforts made to achieve overall peace through the application of the principles of international humanitarian law, crimes against mankind which are of unprecedented concern to the whole world have remained unabated. The fall back on war as a technique for settling disputes between nations, individuals, countries and ethnic groups with accompanying toll of deaths and destruction of properties have remained a conspicuous component of human history. Indeed, to control this conduct of warfare and the dehumanization of individuals, a body of law aimed at regulating the impacts of conflicts and hostilities in the theater of war has become necessary. Thus, it is to examine the conditions in which international humanitarian law will apply and also to determine the extent of the challenges of new progressions of warfare that this study is undertaken. All through this examination, we grasped doctrinal approach wherein we used text books, journals, international materials and supposition of law specialists in the field of international humanitarian law. This paper shall examine the distinctive factors responsible for the rebelliousness to the rules of International Humanitarian Law and furthermore, shall proffer possible courses of action that will address the challenges of new technologies of warfare all over the world. Essentially, the basic proposals made in this paper if totally utilized may go far in ensuring a sufficient standard in the application of the rules of international humanitarian law as it relates to an increasingly frequent phenomenon of contemporary developments in technologies of warfare which has in recent past, made it more difficult for the most ideal application of the rules of international humanitarian law. This paper deduces that for a sustainable global peace to be achieved, the rules of International Humanitarian Law as it relates to the utilization of new technologies of warfare should be completely clung to and should be made a strict liability offense. Likewise, this paper further recommends the introduction of domestic criminal law punishment of serious contraventions of the rules of international humanitarian law.

Keywords: international, humanitarian law, new technologies, warfare

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Authors: Fatemeh Khalili Varnamkhasti

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Natural administration has outside impacts such that companies regularly respect natural input as a fetched with no clear advantage. In this manner, in case natural security can bring financial benefits, showing that natural security and financial interface are in concordance, companies will effectively fulfill their obligation to ensure the environment. Contamination is, for the most part, related to the squandering of assets, misplaced vitality, and crude materials not completely utilized. Contamination avoidance and clean innovation, as inner organizational hones, can offer assistance to play down taken toll and to develop economic aptitudes for the long run, whereas outside organizational hones (item stewardship and maintainability vision) can offer assistance to coordinated partner sees into trade operations and to define future commerce directions. Taken together, these practices can drive shareholder esteem while at the same time contributing to a more feasible world. On the off chance that the company's budgetary execution is nice, it'll draw in financial specialists to contribute and progress the company's execution. In this way, budgetary execution is additionally the determinant of the progression of a company. This can be because the monetary back gotten by the company gets to be the premise for the running of trade forms in the future. Moreover, A green picture can assist firms in pulling in more clients by influencing shopper choices and moving forward with buyer brand dependability. Numerous shoppers need to purchase items from ecologically inviting firms, in spite of the fact that there are, of course, a few who will not pay premium costs for green items.

Keywords: environmental activities, financial performanance, advantage, clients

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Authors: Peter Ned Wales

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This paper is the result of a substantial amount of data looking at how industrially zoned land is changing post COVID in the 21st Century. With the impact of global megatrends such as globalisation, the rapid adaption of innovative technologies and elevated demands on the design typologies, the tradition view of employment lands is quickly evolving. The research findings discussed here clearly show that land use conflicts have begun to take their toll across numerous light industrial precincts within the booming City of the Gold Coast. The recent global pandemic has placed enormous pressures on land values and industrial lands in Southeast Queensland. considered a highly desirable place to live, work and play are morphing in new ways. This region of Australia has become one of the most desirable places to locate after extended pandemic lock downs in Sydney and Melbourne. Findings in the current business trends have highlighted a new way of applying land use zones that provide a sustainable hybrid of acceptable land uses for prosperous business activity. In the wake of a rapid rise in the knowledge economy and boutique products that reflect the younger demographic has resulted in new emerging business activities that are significantly different from business trends two decades ago, when these industrial land use controls were originally applied. This paper explores what are the new demands on these established employment precincts and how local governments can better support start-ups and a broad variety of land uses not previously considered relevant to local government planners.

Keywords: sustainable urban, urban design, industrial lands, employment lands, sustainable communities

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Authors: Razieh Rezabeigi Sani, Alireza Farahani, Mahdi Haghi

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Displacement, local discontent, and forced exclusion have become prominent parts of urban regeneration activities in the Global North and South. This paper discusses the processes of massive displacement and neighborhood alteration as the consequences of a large-scale political/ideological placemaking project in central Tehran that transformed people's daily lives in surrounding neighborhoods. The conversion of Imam Hussein Square and connecting 17-Shahrivar Street to a pedestrian plaza in 2016 resulted in adjacent neighborhoods' physical, social, and economic degradation. The project has downgraded the economic and social characteristics of urban life in surrounding neighborhoods, commercialized residential land uses, displaced local people and businesses, and created unprecedented housing modes. This research has been conducted in two stages; first, after the project's implementation between 2017-2018, and second, when the street was reopened after local protests in 2021. In the first phase, 50+ on-site interviews were organized with planners, managers, and dwellers about the decision-making processes, design, and project implementation. We find that the project was based on the immediate political objectives and top-down power exertion of the local government in creating exclusive spaces (for religious ceremonies) without considering locals' knowledge, preferences, lifestyles, and everyday interactions. In the continued research in 2021, we utilized data gathered in facilitation activities and several meetings and interviews with local inhabitants and businesses to explore, design, and implement initiatives for bottom-up planning in these neighborhoods. The top-down and product-oriented (rather than process-oriented) planning, dependency on municipal financing rather than local partnerships, and lack of public participation proved to have continued effects on local participation. The paper concludes that urban regeneration projects must be based on the participation of different private/public actors, sustainable financial resources, and overall social and spatial analysis of the peripheral area before interventions.

Keywords: displacement, urban regeneration, distressed neighborhoods, ideological placemaking, Tehran

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Authors: Rachmat Mudiyono, Siti Sumiati

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In the next few years, traffic will happen most of the time. This was triggered by the growing rate of vehicles againts the road capacity which is not balance. All the time the congestion in the city of Semarang has been occured at peak hours. Congestion also occured in between Teuku Umar and Setia Budi road Jatingaleh because of a plot intersection (Kesatrian intersection, PLN intersection and Jatingaleh intersection) with the Toll Road. Jatingaleh is located in the southern city of Semarang which is a central meeting point between the upper and lower Semarang where the vehicle flows in through a combination of local current and regional traffic, and the flow of vehicles coming in and out from highway. The main cause of the problems that occurred in the area of Jatingaleh is due to the numbers of vehicles movement that occurs at the intersections. With the above issues, it is necessary to analyse the existing conditions and look into some solutions. Before carrying out an analysis of field surveys at peak hours for example morning (06:00 to 08:00 am) and for the afternoon (04:00 to 06:00 pm)should be conducted, then the number of vehicles is counted manually with “short-breakcounting” according to types of vehicles. From the analysis we found that the degree of saturation (DS) is 1.61 between Teuku Umar and Setia Budi road during the morning peak hours and 1.56 during the afternoon peak hours. This means that the capacity of the existing road is no longer able to accommodate the traffic flow. One of the solutions for the congestion that occurs at the intersection of Jatingaleh is to apply the efficiency of the intersection that is not in a plot with a Fly over, Underpass and the combination of Fly Over-Underpass. Base on the flow reduction calculation with 3 comparative modeling it shows that the Fly Over is the most technically efficient to be applied in this research.

Keywords: single fly over, congestion, intersection, interchange

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Authors: Repaul Kanji, Rajat Agrawal

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In this era where issues like climate change and disasters are the topics of discussion at national and international forums, it is very often that humanity questions the causative role of corporates in such events. It is beyond any doubt that rapid industrialisation and development has taken a toll in the form of climate change and even disasters, in some case. Thus, demanding to fulfill a corporate's responsibilities in the form of rescue and relief in times of disaster, rehabilitation and even mitigation and preparedness to adapt to the oncoming changes is obvious. But how can the responsibilities of the corporates be channelised to ensure all this, i.e., develop a resilient society? More than that, which factors, when emphasised upon, can lead to the holistic development of the society. To answer this query, an extensive literature review was done to identify several enablers like legislations of a nation, the role of brand and reputation, ease of doing Corporate Social Responsibility, mission and vision of an organisation, religion and culture, etc. as a tool for building disaster resilience. A questionnaire survey, interviews with experts and academicians followed by interpretive structural modelling (ISM) were used to construct a multi-hierarchy model depicting the contextual relationship among the identified enablers. The study revealed that culture and religion are the most powerful driver, which affects other enablers either directly or indirectly. Taking cognisance of the fact that an idea of separation between religion and workplace (business) resides subconsciously within the society, the study tries to interpret the outcome of the ISM through the lenses of past researches (The Integrating Box) and explores how it can be leveraged to build a resilient society.

Keywords: corporate social responsibility, interpretive structural modelling, disaster resilience and risk reduction, the integration box (TIB)

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Authors: Kaesha M. Freyaldenhoven

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Chicago is a city in the United States whose cultural identity is largely shaped by public art pieces. Quintessential public works created by internationally renown artists – such as Anish Kapoor’s Cloud Gate in Millennium Park and 'The Picasso' in Daley Plaza – have historically contributed to developing a shared sense of community. In 2017, the city implemented a policy titled 50x50 Neighborhood Arts Project under the Chicago Public Art Plan. The policy promotes investments in contemporary public art to elevate neighborhood cultural assets and create a sense of place. Exclusively community-based artists were commissioned to accomplish the mission of the policy. Administrators felt only local artists would be capable of capturing the true essence of a neighborhood through art. This paper discusses the relationship between the public art and the culture of its respective neighborhood through close examination of aesthetic formal properties and social significance. Research compares the role of international artists with the role of local artists in cultivating the identity of a city through site-specific artworks in Chicago. Methodology unites theoretical research on understanding art and its function in the public space with empirical research on Chicago-based works. Theoretical frameworks provide an art historical foundation to explore the manner in which physical properties convey meaning through the work itself and its placement in an urban setting. Empirical research that examines policy documentation and press announcements released by the Department of Cultural Affairs and Special Events investigates project selection processes pertaining to the artists and neighborhoods. Ethnographies and interviews of individuals from diverse social segments in contemporary Chicago society measure impacts of the works on respective populations. Findings demonstrate works created by local artists activate neighborhoods and inculcate a sense of pride among community residents. Works created by international artists garner widespread media attention that frames the city’s cultural identity across temporal and geographic zones. This research can be utilized to inform future cultural policies pertaining to the commission of public art.

Keywords: Chicago, cultural policy, public art, urban art

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Authors: Jacob Medupe

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Life as we know it has changed since the global outbreak of Coronavirus Disease 2019 (COVID-19) and business as usual will not continue. The human impact of the COVID-19 crisis is already immeasurable. Moreover, COVID-19 has already negatively impacted economies, livelihoods and disrupted food systems around the world. The disruptive nature of the Corona virus has affected every sphere of life including the culture and teaching and learning. Right now the majority of education research is based around classroom management techniques that are no longer necessary with digital delivery. Instead there is a great need for new data about how to make the best use of the one-on-one attention that is now becoming possible (Diamandis & Kotler, 2014). The COVID-19 pandemic has necessitated an environment where the South African learners are focused to adhere to social distancing in order to minimise the wild spread of the Corona virus. This arrangement forces the student to utilise the online classroom technologies to continue with the lessons. The historical reality is that the country has not made much strides on the closing of the digital divide and this is particularly a common status quo in the deep rural areas. This will prove to be a toll order for most of the learners affected by the Corona Virus to be able to have a seamless access to the online learning facilities. The paper will seek to look deeply into this reality and how the Corona virus has brought us to the reality that South Africa remains a deeply unequal society in every sphere of life. The study will also explore the state of readiness for education system around the online classroom environment.

Keywords: virtual learning, virtual classroom, COVID-19, Corona virus, internet connectivity, blended learning, online learning, distance education, e-learning, self-regulated Learning, pedagogy, digital literacy

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Authors: Ortega Ivan, De La Plaza Edurne

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Background: Spain and other European countries have implemented Uncontrolled Donation after Cardiac Death (uDCD) programs. After 15 years of experience in Spain, many things have changed. Recent evidence and technical breakthroughs achieved in resuscitation are relevant for uDCD programs and raise some ethical concerns related to these protocols. Aim: To rethink current uDCD programs in the light of recent evidence on available therapeutic procedures applicable to victims of out-of-hospital cardiac arrest (OHCA). To address the following question: What is the current standard of treatment owed to victims of OHCA before including them in an uDCD protocol? Materials and Methods: Review of the scientific and ethical literature related to both uDCD programs and innovative resuscitation techniques. Results: 1) The standard of treatment received and the chances of survival of victims of OHCA depend on whether they are classified as Non-Heart Beating Patients (NHBP) or Non-Heart-Beating-Donors (NHBD). 2) Recent studies suggest that NHBPs are likely to survive, with good quality of life, if one or more of the following interventions are performed while ongoing CPR -guided by suspected or known cause of OHCA- is maintained: a) direct access to a Cath Lab-H24 or/and to extra-corporeal life support (ECLS); b) transfer in induced hypothermia from the Emergency Medical Service (EMS) to the ICU; c) thrombolysis treatment; d) mobile extra-corporeal membrane oxygenation (mini ECMO) instituted as a bridge to ICU ECLS devices. 3) Victims of OHCA who cannot benefit from any of these therapies should be considered as NHBDs. Conclusion: Current uDCD protocols do not take into account recent improvements in resuscitation and need to be adapted. Operational criteria to distinguish NHBDs from NHBP should seek a balance between the technical imperative (to do whatever is possible), considerations about expected survival with quality of life, and distributive justice (costs/benefits). Uncontrolled DCD protocols can be performed in a way that does not hamper the legitimate interests of patients, potential organ donors, their families, the organ recipients, and the health professionals involved in these processes. Families of NHBDs’ should receive information which conforms to the ethical principles of respect of autonomy and transparency.

Keywords: uncontrolled donation after cardiac death resuscitation, refractory cardiac arrest, out of hospital cardiac, arrest ethics

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Authors: Manal Anis, Bin Bakhti Sayeed

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With the encroachment of automobile upon our communities for decades and the concomitant urban sprawl resulting in a loss of public place, it was only a matter of time before people, realizing the role of streets in stimulating urban prosperity, would start reclaiming them to rebuild their communities. In order for this restoration of communities to take effect it is imperative that streets be freed from the dominance of motor vehicles. A holistic approach to pedestrian-friendly street environment can help build communities that embody the cities in which they are found. While the developed countries are finding more and more innovative ways to integrate walkable streets to foster communal living, the developing countries still have a long way to go. Since Dhaka is still struggling to balance the growing needs of accommodating automobiles for increased population with the loss of urban community life that comes with it, it is high time that alternate approaches are looked into. This study aims to understand streets as a living corridor through which one discovers and identifies with the city. The research area is chosen to be Manik Mia Avenue, overlooking the South Plaza of the National Parliament Building in Dhaka city. Being the site of supreme power, it is precisely this symbolic importance that the National Parliament Building has in the psyche of Bangladeshis, which has given Manik Mia Avenue a significant place in the country’s history. Above all, being an avenue it is essentially a neutral territory, universally accessible, inclusive and pluralist. The needs of the Avenue’s frequent users are analyzed with the help of a multi-method approach to survey consisting of an empirical study, a questionnaire survey and interview with relevant users. The research then tries to understand the concept of walkability by exploring the different ways in which the built environment influences walking. For this analysis, the six dimensions of Matthew Carmona are taken as a guideline for a holistic approach toward the different interacting facets of an urban public space. Based on the studies, a set of criteria is proposed to evaluate, plan and design streets that are more contextual in nature. The study concludes with how the existing street patterns of Dhaka city can be rethought and redesigned to cater to peoples’ need for a public place. The proposal is meant to be an inspiration for further studies in this respect in the context of Bangladesh.

Keywords: public space, six dimensions, street, urban, walkability

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

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

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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Authors: Aryan Sood, Shruti Pathak, Dipanshu Chaudhary, Shreyanshi, Yogesh Pal

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In this comprehensive meta-analysis, the study delves into the widespread issue of body shaming, revealing its pervasive impact on various aspects of human life and its profound implications for mental health. The paper first explores the origins of body shaming, including societal norms, media influences, and interpersonal dynamics. It highlights the various forms it takes and its detrimental effects on self-esteem, body image, and psychological well-being. Particularly among adolescents and teenagers in today's social media-driven world, the pressure to conform to idealized beauty standards is significant, leading to negative consequences for their development and health. The research emphasizes the long-lasting mental health effects of body shaming, including depression, body dysmorphia, low self-esteem, and eating disorders. The study also discusses the emergence of body positivity movements as a means to challenge societal norms and promote inclusivity and empathy. Furthermore, the research addresses body shaming in the workplace and presents strategies to combat it, stressing the importance of awareness campaigns, education, and policy changes. In conclusion, the study underscores the critical need for a culture of acceptance and support, the promotion of positive body image, and efforts to mitigate the severe mental health toll that body shaming takes on individuals and communities. Overall, this research provides a comprehensive overview of body shaming, its root causes, and its far-reaching impacts on mental health and well-being. It highlights the urgency of addressing this issue in various contexts, from adolescence to the workplace, and offers solutions, such as awareness campaigns and societal changes, to foster a more inclusive and empathetic future.

Keywords: body shaming, mental health, age, gender, societal norms, appearance-based discrimination, cyberbullying, self-esteem, social media, depression, acceptance

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Authors: Sitarrine Thongpussawal, Dasarath Jayasuriya, Thanaroj Woraratprasert, Sakawtree Prajamwong

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Thailand grapples with recurrent floods causing substantial repercussions on its economy, society, and environment. In 2021, the economic toll of these floods amounted to an estimated 53,282 million baht, primarily impacting the agricultural sector. The existing flood monitoring system in Thailand suffers from inaccuracies and insufficient information, resulting in delayed warnings and ineffective communication to the public. The Office of the National Water Resources (OWNR) is tasked with developing and integrating data and information systems for efficient water resources management, yet faces challenges in monitoring accuracy, forecasting, and timely warnings. This study endeavors to evaluate the viability of enhancing Thailand's Flood Forecasting and Warning (FFW) systems. Additionally, it aims to formulate a comprehensive work package grounded in international best practices to enhance the country's FFW systems. Employing qualitative research methodologies, the study conducted in-depth interviews and focus groups with pertinent agencies. Data analysis involved techniques like note-taking and document analysis. The study substantiates the feasibility of developing and enhancing FFW systems in Thailand. Implementation of international best practices can augment the precision of flood forecasting and warning systems, empowering local agencies and residents in high-risk areas to prepare proactively, thereby minimizing the adverse impact of floods on lives and property. This research underscores that Thailand can feasibly advance its FFW systems by adopting international best practices, enhancing accuracy, and improving preparedness. Consequently, the study enriches the theoretical understanding of flood forecasting and warning systems and furnishes valuable recommendations for their enhancement in Thailand.

Keywords: flooding, forecasting, warning, monitoring, communication, Thailand

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Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

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A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

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Introduction: Tuberculosis (TB) is a known disease with hidden features caused by Mycobacterium tuberculosis (MTB). This disease, which is one of the 10 deadliest in the world, has caused millions of deaths in recent decades. Furthermore, TB is responsible for infecting about 30% population of world. Like any infection, TB can activate the immune system by locating and colonization in the human body, especially in the alveoli. TB is granulomatosis, so MTB can absorb the host’s immune cells and other cells to form granuloma. Method: Different databases (e.g., PubMed) were recruited to prepare this paper and fulfill our goals to search and find effective papers and investigations. Results: Immune response to MTB is related to T cell killers and contains CD1, CD4, and CD8 T lymphocytes. CD1 lymphocytes can recognize glycolipids, which highly exist in the Mycobacterial fatty cell wall. CD4 lymphocytes and macrophages form granuloma, and it is the main line of immune response to Mycobacteria. On the other hand, CD8 cells have cytolytic function for directly killing MTB by secretion of granulysin. Other functions and secretion to the deal are interleukin-12 (IL-12) by induction of expression interferon-γ (INF-γ) for macrophages activation and creating a granuloma, and tumor necrosis factor (TNF) by promoting macrophage phagolysosomal fusion. Conclusion: Immune cells in battle with MTB are macrophages, dendritic cells (DCs), neutrophils, and natural killer (NK) cells. These immune cells can recognize the Mycobacterium by various receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and C-type lectin receptors (CLRs) located in the cell surface. In human alveoli exist about 50 dendritic macrophages, which have close communication with other immune cells in the circulating system and epithelial cells to deal with Mycobacteria. Against immune cells, MTB handles some factors (e.g., cordfactor, O-Ag, lipoarabinomannan, sulfatides, and adenylate cyclase) and practical functions (e.g., inhibition of macrophages).

Keywords: mycobacterium tuberculosis, immune responses, immunological mechanisms, respiratory tuberculosis

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Authors: Maria Pratt, Lynn Martin

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Context: In nursing education, clinical instructors are crucial in assessing and evaluating students' performance in clinical courses. However, instructors often struggle when assigning failing grades to students at risk of failing. Research Aim: This qualitative study aims to understand clinical instructors' experiences evaluating students with unsatisfactory performance, including how reflection and collegial support impact this evaluation process. Methodology, Data Collection, and Analysis Procedures: This study employs Gadamer's Hermeneutic Inquiry as the research methodology. A purposive maximum variation sampling technique was used to recruit eight clinical instructors from a collaborative undergraduate nursing program in Southwestern Ontario. Semi-structured, open-ended, and audio-taped interviews were conducted with the participants. The hermeneutic analysis was applied to interpret the interview data to allow for a thorough exploration and interpretation of the instructors' experiences evaluating failing students. Findings: The main findings of this qualitative research indicate that evaluating failing students was emotionally draining for the clinical instructors who experienced multiple challenges, uncertainties, and negative feelings associated with assigning failing grades. However, the analysis revealed that ongoing reflection and collegial support played a crucial role in mitigating the challenges they experienced. Conclusion: This study contributes to the theoretical understanding of nursing education by shedding light on clinical instructors' challenges in evaluating failing students. It emphasizes the emotional toll associated with this process and the role that reflection and collegial support play in alleviating those challenges. The findings underscore the need for ongoing professional development and support for instructors in nursing education. By understanding and addressing clinical instructors' experiences, nursing education programs can better equip them to effectively evaluate struggling students and provide the necessary support for their professional growth.

Keywords: clinical instructor, student evaluation, nursing, reflection, support

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Authors: Zhuo Feng, Ying Gao

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Public-private partnership (PPP), as an innovative way to provide infrastructures by the private sector, is being widely used throughout the world. Compared with the traditional mode, PPP emerges largely for merits of relieving public budget constraint and improving infrastructure supply efficiency by involving private funds. However, PPP projects are characterized by large scale, high investment, long payback period, and long concession period. These characteristics make PPP projects full of risks. One of the most important risks faced by the private sector is demand risk because many factors affect the real demand. If the real demand is far lower than the forecasting demand, the private sector will be got into big trouble because operating revenue is the main means for the private sector to recoup the investment and obtain profit. Therefore, it is important to study how the government compensates the private sector when the demand risk occurs in order to achieve Pareto-improvement. This research focuses on price compensation mechanism, an ex-post compensation mechanism, and analyzes, by mathematical modeling, the impact of price compensation mechanism on payoff of the private sector and consumer surplus for PPP toll road projects. This research first investigates whether or not price compensation mechanisms can obtain Pareto-improvement and, if so, then explores boundary conditions for this mechanism. The research results show that price compensation mechanism can realize Pareto-improvement under certain conditions. Especially, to make the price compensation mechanism accomplish Pareto-improvement, renegotiation costs of the government and the private sector should be lower than a certain threshold which is determined by marginal operating cost and distortionary cost of the tax. In addition, the compensation percentage should match with the price cut of the private investor when demand drops. This research aims to provide theoretical support for the government when determining compensation scope under the price compensation mechanism. Moreover, some policy implications can also be drawn from the analysis for better risk-sharing and sustainability of PPP projects.

Keywords: infrastructure, price compensation mechanism, public-private partnership, renegotiation

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Authors: Junaid Jibran Jawed, Prasanta Saini, Subrata Majumdar

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Background: Leishmania donovani infection causes severe host immune-suppression through the modulation of pathogen recognition receptors. Apart from TLRs (Toll Like Receptor), recent studies focus on the important contribution of NLR (NOD-Like Receptor) family member NOD1 and NOD2 as these receptors are capable of triggering host innate immunity. The aim of this study was to decipher the role of NOD1/NOD2 receptors during experimental visceral leishmaniasis (VL) and the important link between host failure and parasite evasion strategy. Method: The status of NOD1 and NOD2 receptors were analysed in uninfected and infected cells through western blotting and RT-PCR. The active contributions of these receptors in reducing parasite burden were confirmed by siRNA mediated silencing, and over-expression studies and the parasite numbers were calculated through microscopic examination of the Giemsa-stained slides. In-vivo studies were done by using non-toxic dose of Mw (Mycobacterium indicus pranii), Ara-LAM(Arabinoasylated lipoarabinomannan) along with MDP (Muramyl dipeptide) administration. Result: Leishmania donovani infection of the macrophages reduced the expression of NOD2 receptors whereas NOD1 remain unaffected. MDP, a NOD2-ligand, treatment during over-expression of NOD2, reduced the parasite burden effectively which was associated with increased pro-inflammatory cytokine generation and NO production. In experimental mouse model, Ara-LAM treatment increased the expression of NOD2 and in combination with MDP it showed active therapeutic potential against VL and found to be more effective than Mw which was already reported to be involved in NOD2 modulation. Conclusion: This work explores the essential contribution of NOD2 during experimental VL and mechanistic understanding of Ara-LAM + MDP combination therapy to work against this disease and highlighted NOD2 as an essential therapeutic target.

Keywords: Ara-LAM (Arabinoacylated Lipoarabinomannan), NOD2 (nucleotide binding oligomerization receptor 2), MDP (muramyl di peptide), visceral Leishmaniasis

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Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

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This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

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Authors: Israel B. Bitton

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“Memory” is associated with various phenomena, from physical to mental, personal to collective and historical to cultural. As part of a broader exploration of memory studies in philosophy and science (slated for academic publication October 2021), this specific study employs analytical methods of cognitive psychology and philosophy of memory to theorize that A) the primary human will (drive) is to significance, in that every human action and expression can be rooted in a most primal desire to be cosmically significant (however that is individually perceived); and B) that the will to significance manifests as the will to memorability, an innate desire to be remembered by others after death. In support of these broad claims, a review of various popular culture “touchpoints”—historic and contemporary records spanning literature, film and television, traditional news media, and social media—is presented to demonstrate how this very theory is repeatedly and commonly expressed (and has been for a long time) by many popular public figures as well as “everyday people.” Though developed before COVID, the crisis only increased the theory’s relevance: so many people were forced to die alone, leaving them and their loved ones to face even greater existential angst than what ordinarily accompanies death since the usual expectations for one’s “final moments” were shattered. To underscore this issue of, and response to, what can be considered a sociocultural “memory gap,” this study concludes with a summary of several projects launched by journalists at the height of the pandemic to document the memorable human stories behind COVID’s tragic warped speed death toll that, when analyzed through the lens of Viktor E. Frankl’s psychoanalytical perspective on “existential meaning,” shows how countless individuals were robbed of the last wills and testaments to their self-significance and memorability typically afforded to the dying and the aggrieved. The resulting insight ought to inform how government and public health officials determine what is truly “non-essential” to human health, physical and mental, at times of crisis.

Keywords: cognitive psychology, covid, neuroscience, philosophy of memory

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Authors: Thomais Tsoulia, Arvind Y. M. Sundaram, Stine Braaen, Øyvind Haugland, Espen Rimstad, Øystein Wessel, Maria K. Dahle

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Fish red blood cells (RBC) are nucleated, and in addition to their function in gas exchange, they have been characterized as mediators of immune responses. Salmonid RBC are the major target cells of Piscineorthoreovirus (PRV), a virus associated with heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. The activation of antiviral response genesin RBChas previously been described in ex vivo and in vivo PRV-infection models, but not explored in the initial virus encounter phase. In the present study, mRNA transcriptome responses were explored in erythrocytes from individual fish, kept ex vivo, and exposed to purified PRV for 24 hours. The responses were compared to responses in macrophage-like salmon head kidney (SHK-1) and endothelial-like Atlantic salmon kidney (ASK) cells, none of which support PRV replication. The comparative analysis showed that the antiviral response to PRV was strongest in the SHK-1 cells, with a set of 80 significantly induced genes (≥ 2-fold upregulation). In RBC, 46 genes were significantly upregulated, while ASK cells were not significantly responsive. In particular, the transcriptome analysis of RBC revealed that PRV significantly induced interferon regulatory factor 1 (IRF1) and interferon-induced protein with tetratricopeptide repeats 5-like (IFIT9). However, several interferon-regulated antiviral genes which have previously been reported upregulated in PRV infected RBC in vivo (myxovirus resistance (Mx), interferon-stimulated gene 15 (ISG15), toll-like receptor 3 (TLR3)), were not significantly induced after 24h of virus stimulation. In contrast to RBC, these antiviral response genes were significantly upregulated in SHK-1. These results confirm that RBC are involved in the innate immune response to viruses, but with a delayed antiviral response compared to SHK-1. A notable difference is that interferon regulatory factor 1 (IRF-1) is the most strongly induced gene in RBC, but not among the significantly induced genes in SHK-1. Putative differences in the binding, recognition, and response to PRV, and any link to effects on the ability of PRV to replicate remains to be explored.

Keywords: antiviral responses, atlantic salmon, piscine orthoreovirus-1, red blood cells, RNA-seq

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Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Lakshmi Chebolu

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'War’, the word itself, is so vibrant and handcuffs the entire society. Since the beginning of manhood, the world has been evident in constant struggles. However, along with the growth of communities, relations, on the one hand, and disputes, on the other hand, infinitely increased. When states cannot or will not settle their disputes or differences by means of peaceful agreements, weapons are suddenly made to speak. It does not mean states can engage in war whenever they desire. At an international level, there has been a vast development of the law of war in the 20th century. War, it may be internal or international, in all situations, belligerent actors should follow the principles of warfare. With the advent of technology, the shape of war has changed, and it violates fundamental principles without observing basic norms. Conversely, states' attitudes towards international relationships are also undermined to some extent as state parties are not prioritized the communal interest rather than political or individual interest. In spite of the persistent development of communities, still many people are innocent victims of modern wars. It costs a toll on many lives, liberties, and properties and remains a major obstacle to nations' development. Recent incidents in Afghan are a live example to World Nations. We know that the principles of international law cannot be implemented very strictly on perpetrators due to the lacuna in the international legal system. However, the rules of war are universal in nature. The Geneva Convention, 1949 which are the core element of IHL, has been ratified by all 196 States. In fact, very few international treaties received this much of big support from nations. State’s approach towards Modern International Law, places a heavy burden on States practice towards in implementation of law. Although United Nations Security Council possesses certain powers under ‘Pacific Settlement of Disputes’, (Chapter VI) of the United Nations Charter to prevent disputes in a peaceful manner, conversely, this practice has been overlooked for many years due to political interests, favor, etc. Despite international consensus on the prohibition of war and protection of fundamental freedoms and human dignity, still, often, law has been misused by states’. The recent tendencies trigger questions about states’ willingness towards the implementation of the law. In view of the existing practices of nations, this paper aims to elevate the legal obligations of the international community to save the succeeding generations from the scourge of modern war practices.

Keywords: modern wars, weapons, prohibition and suspension of war activities, states’ obligations

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Authors: Keith T. S. Tung, H. W. Tsang, Rosa S. Wong, Frederick K. Ho, Patrick Ip

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Objectives: Atopic diseases are increasingly prevalent among children and adolescents, both locally and internationally. One of the possible contributing factors could be the hypercholesterolemia which leads to cholesterol accumulation in macrophages and other immune cells that would eventually promote inflammatory responses, including augmentation of toll-like receptor (TLR). Meanwhile, physical activity is well known for its beneficial effects against the condition of hypercholesterolemia and incidence of atopic diseases. This study, therefore, explored whether atopic diseases were associated with increased cholesterol levels and whether physical activity habit influenced this association. Methods: This is a sub-study derived from the longitudinal cohort study which recruited a group of children at five years of age in Kindergarten 3 (K3) to investigate the long-term impact of family socioeconomic status on child development. In 2018/19, adolescents (average age: 13 years old) were asked to report their physical activity habit and history of any atopic diseases. During health assessment, peripheral blood samples were collected from the adolescents to study their lipid profile [total cholesterol, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol]. Regression analyses were performed to test the relationships between variables of interest. Results: Among the 315 adolescents, 99 (31.4%) reported to have allergic rhinitis. There were 45 (14.3%) with eczema, 17 (5.4%) with a food allergy, and 12 (3.8%) with asthma. Regression analyses showed that adolescents with a history of any type of atopic diseases had significantly higher total cholesterol (B=13.3, p < 0.01) and LDL cholesterol (B=7.9, p < 0.05) levels. Further subgroup analyses were conducted to examine the effect of physical activity level on the association between atopic diseases and cholesterol levels. We found stronger associations among those who did not meet the World Health Organization recommendation of at least 60 minutes of moderate-to-vigorous activities each day (total cholesterol: B=15.5, p < 0.01; LDL cholesterol: B=10.4, p < 0.05). For those who met this recommendation, the associations between atopic diseases and cholesterol levels became insignificant. Conclusion: Our study results support the current research evidence on the relationship between an elevated level of cholesterol and atopic diseases. More importantly, our results provide preliminary support for the protective effect of regular exercises against elevated cholesterol level due to atopic diseases. The findings highlight the importance of a healthy lifestyle for keeping cholesterol levels in the normal range, which can bring benefits to both physical and mental health.

Keywords: atopic diseases, Chinese adolescents, cholesterol level, physical activity

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Authors: C. Fernandez-Plaza, I. Abad, E. Diaz, I. Diaz

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Births occurring before the 37th week of gestation are considered preterm births. A threat of preterm is defined as the beginning of regular uterine contractions, dilation and cervical effacement between 23 and 36 gestation weeks. To author's best knowledge, the factors that determine the beginning of the birth are not completely defined yet. In particular, the incidence of sleep habits on preterm births is weekly studied. The aim of this study is to develop a model to predict the factors affecting premature delivery on pregnancy, based on the above potential risk factors, including those derived from sleep habits and light exposure at night (introduced as 12 variables obtained by a telephone survey using two questionnaires previously used by other authors). Thus, three groups of variables were included in the study (maternal, fetal and sleep habits). The study was approved by Research Ethics Committee of the Principado of Asturias (Spain). An observational, retrospective and descriptive study was performed with 481 births between January 1, 2015 and May 10, 2016 in the University Central Hospital of Asturias (Spain). A statistical analysis using SPSS was carried out to compare qualitative and quantitative variables between preterm and term delivery. Chi-square test qualitative variable and t-test for quantitative variables were applied. Statistically significant differences (p < 0.05) between preterm vs. term births were found for primiparity, multi-parity, kind of conception, place of residence or premature rupture of membranes and interruption during nights. In addition to the statistical analysis, machine learning methods to look for a prediction model were tested. In particular, tree based models were applied as the trade-off between performance and interpretability is especially suitable for this study. C5.0, recursive partitioning, random forest and tree bag models were analysed using caret R-package. Cross validation with 10-folds and parameter tuning to optimize the methods were applied. In addition, different noise reduction methods were applied to the initial data using NoiseFiltersR package. The best performance was obtained by C5.0 method with Accuracy 0.91, Sensitivity 0.93, Specificity 0.89 and Precision 0.91. Some well known preterm birth factors were identified: Cervix Dilation, maternal BMI, Premature rupture of membranes or nuchal translucency analysis in the first trimester. The model also identifies other new factors related to sleep habits such as light through window, bedtime on working days, usage of electronic devices before sleeping from Mondays to Fridays or change of sleeping habits reflected in the number of hours, in the depth of sleep or in the lighting of the room. IF dilation < = 2.95 AND usage of electronic devices before sleeping from Mondays to Friday = YES and change of sleeping habits = YES, then preterm is one of the predicting rules obtained by C5.0. In this work a model for predicting preterm births is developed. It is based on machine learning together with noise reduction techniques. The method maximizing the performance is the one selected. This model shows the influence of variables related to sleep habits in preterm prediction.

Keywords: machine learning, noise reduction, preterm birth, sleep habit

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Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

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Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

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Authors: Supanan Chansap, Werachon Cheukamud, Pornanan Kueakhai, Narin Changklungmoa

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Fasciola species (Fasciola spp.) is caused fasciolosis in ruminants such as cattle, sheep, and buffalo. Fasciola gigantica (F.gigantica) commonly infects tropical regions. Fasciola hepatica (F.hepatica) in temperate regions. Liver fluke infection affects livestock economically, for example, reduced milk and meat production, weight loss, sterile animals. Currently, Triclabendazole is used to treat liver flukes. However, liver flukes have also been found to be resistant to drugs in countries. Therefore, vaccination is an attractive alternative to prevent liver fluke infection. Peptide vaccines are new vaccine technologies that mimic epitope antigens that trigger an immune response. An interesting antigen used in vaccine production is catepsin L, a family of proteins that play an important role in the life of the parasite in the host. This study aims to identify immunogenic regions of protein and construct a multi-epidetope vaccine using an immunoinformatic tool. Fasciola gigantica Cathepsin L1 (FgCatL1), Fasciola gigantica Cathepsin L1G (FgCatL1G), and Fasciola gigantica Cathepsin L1H (FgCatL1H) were predicted B-cell and Helper T lymphocytes (HTL) by Immune Epitope and Analysis Resource (IEDB) servers. Both B-cell and HTL epitopes aligned with cathepsin L of the host and Fasciola hepatica (F. hepatica). Epitope groups were selected from non-conserved regions and overlapping sequences with F. hepatica. All overlapping epitopes were linked with the GPGPG and KK linker. GPGPG linker was linked between B-cell epitope. KK linker was linked between HTL epitope and B-cell and HTL epitope. The antigenic scores of multi-epitope peptide vaccine was 0.7824. multi-epitope peptide vaccine was non-allergen, non-toxic, and good soluble. Multi-epitope peptide vaccine was predicted tertiary structure and refinement model by I-Tasser and GalaxyRefine server, respectively. The result of refine structure model was good quality that was generated by Ramachandran plot analysis. Discontinuous and linear B-cell epitopes were predicted by ElliPro server. Multi-epitope peptide vaccine model was two and seven of discontinuous and linear B-cell epitopes, respectively. Furthermore, multi-epitope peptide vaccine was docked with Toll-like receptor 2 (TLR-2). The lowest energy ranged from -901.3 kJ/mol. In summary, multi-epitope peptide vaccine was antigenicity and probably immune response. Therefore, multi-epitope peptide vaccine could be used to prevent F. gigantica infections in the future.

Keywords: fasciola gigantica, Immunoinformatic tools, multi-epitope, Vaccine

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