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Authors: Mohua Dutta

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The primary aim of this research paper is to investigate the forced urban migration of Dalits in India who are fleeing caste persecution in rural areas. This paper examines the relationship between caste and rural-to-urban internal migration in India using a literary text, Rohinton Mistry’s A Fine Balance, highlighting the challenges faced by Dalits in rural areas that force them to migrate to urban areas. Despite the prevalence of such discussions in Dalit autobiographies written in vernacular languages, there is a lack of discussion regarding caste migration in Indian English Literature, including this present text, as evidenced by the existing critical interpretations of the novel, which this paper seeks to rectify. The primary research question is how urban migration affects caste system in India and why rural-to-urban caste migration occurs. The purpose of this paper is to better understand the reasons for Dalit migration, the challenges they face in rural and urban areas, and the lingering influence of caste in both rural and urban areas. The study reveals that the promise of mobility and emancipation provided by class operations drives rural-to-urban caste migration in India, but it also reveals that caste marginalization in rural areas is closely linked to class marginalization and other forms of subalternity in urban areas. Moreover, the caste system persists in urban areas as well, making Dalit migrants more vulnerable to social, political, and economic discrimination. The reason for this is that, despite changes in profession and urban migration, the trapped structure of caste capital and family networks exposes migrants to caste and class oppressions. To reach its conclusion, this study employs a variety of methodologies. Discourse analysis is used to investigate the current debates and narratives surrounding caste migration. Critical race theory, specifically intersectional theory and social constructivism, aids in comprehending the complexities of caste, class, and migration. Mistry's novel is subjected to textual analysis in order to identify and interpret references to caste migration. Secondary data, such as theoretical understanding of the caste system in operation and scholarly works on caste migration, are also used to support and strengthen the findings and arguments presented in the paper. The study concludes that rural-to-urban caste migration in India is primarily motivated by the promise of socioeconomic mobility and emancipation offered by urban spaces. However, the caste system persists in urban areas, resulting in the continued marginalisation and discrimination of Dalit migrants. The study also highlights the limitations of urban migration in providing true emancipation for Dalit migrants, as they remain trapped within caste and family network structures. Overall, the study raises awareness of the complexities surrounding caste migration and its impact on the lives of India's marginalised communities. This study contributes to the field of Migration Studies by shedding light on an often-overlooked issue: Dalit migration. It challenges existing literary critical interpretations by emphasising the significance of caste migration in Indian English Literature. The study also emphasises the interconnectedness of caste and class, broadening understanding of how these systems function in both rural and urban areas.

Keywords: rural-to-urban caste migration in india, internal migration in india, caste system in india, dalit movement in india, rooster coop of caste and class, urban poor as subalterns

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Authors: Beste Ozcan, Valerio Sperati, Laura Romano, Tania Moretta, Simone Scaffaro, Noemi Faedda, Federica Giovannone, Carla Sogos, Vincenzo Guidetti, Gianluca Baldassarre

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+me is an experimental interactive toy with the appearance of a soft, pillow-like, panda. Shape and consistency are designed to arise emotional attachment in young children: a child can wear it around his/her neck and treat it as a companion (i.e. a transitional object). When caressed on paws or head, the panda emits appealing, interesting outputs like colored lights or amusing sounds, thanks to embedded electronics. Such sensory patterns can be modified through a wirelessly connected tablet: by this, an adult caregiver can adapt +me responses to a child's reactions or requests, for example, changing the light hue or the type of sound. The toy control is therefore shared, as it depends on both the child (who handles the panda) and the adult (who manages the tablet and mediates the sensory input-output contingencies). These features make +me a potential tool for therapy with children with Neurodevelopmental Disorders (ND), characterized by impairments in the social area, like Autism Spectrum Disorders (ASD) and Language Disorders (LD): as a proposal, the toy could be used together with a therapist, in rehabilitative play activities aimed at encouraging simple social interactions and reinforcing basic relational and communication skills. +me was tested in two pilot experiments, the first one involving 15 Typically Developed (TD) children aged in 8-34 months, the second one involving 7 children with ASD, and 7 with LD, aged in 30-48 months. In both studies a researcher/caregiver, during a one-to-one, ten-minute activity plays with the panda and encourages the child to do the same. The purpose of both studies was to ascertain the general acceptability of the device as an interesting toy that is an object able to capture the child's attention and to maintain a high motivation to interact with it and with the adult. Behavioral indexes for estimating the interplay between the child, +me and caregiver were rated from the video recording of the experimental sessions. Preliminary results show how -on average- participants from 3 groups exhibit a good engagement: they touch, caress, explore the panda and show enjoyment when they manage to trigger luminous and sound responses. During the experiments, children tend to imitate the caregiver's actions on +me, often looking (and smiling) at him/her. Interesting behavioral differences between TD, ASD, and LD groups are scored: for example, ASD participants produce a fewer number of smiles both to panda and to a caregiver with respect to TD group, while LD scores stand between ASD and TD subjects. These preliminary observations suggest that the interactive toy +me is able to raise and maintain the interest of toddlers and therefore it can be reasonably used as a supporting tool during therapy, to stimulate pivotal social skills as imitation, turn-taking, eye contact, and social smiles. Interestingly, the young age of participants, along with the behavioral differences between groups, seem to suggest a further potential use of the device: a tool for early differential diagnosis (the average age of a child

Keywords: autism spectrum disorders, interactive toy, social interaction, therapy, transitional wearable companion

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Authors: Eleftheria Atta, Yianna Vovides, Marios Katsioloudes

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In the fusion of neoliberalism and globalization, Higher Education (HE) is becoming increasingly complex. The changing patterns of the economy worldwide caused the development of high value-added economy HE has been viewed as a social investment, significant for the development of knowledge-based societies and economies. In order to contribute to economic competitiveness universities are required to produce local and employable workers in order to fit into the neoliberal economic environment. The emergence of neoliberal performativity, which measures outcomes, is a key aspect in a neoliberal era. It facilitates the redesign of institutions making organizations and individuals to think about themselves in relation to their performance. Performativity and performance management systems lead academics to become more effective, professionally advance, improve and become better than others and therefore act competitively. Besides the aforementioned complexities, universities also encounter the challenge of maintaining a set of values to guide an institution’s actions and which have always been highly respected in developing a HE institution. The formulation of a clear set of values also determines the institutional culture which will be maintained. It is evident that values create a significant framework for the workplace and may determine positive institutional results. Universities are required to engage in activities for capacity building which will improve their students’ competence as well as offer opportunities to administrative and academic staff to professionally develop in light of neoliberal performativity. Additionally, the University is now considered as an innovation ecosystem playing a significant role in providing education, research and innovation to help create solutions to meet social, environmental and economic challenges. Thus, Universities become central in orchestrating multi-actor innovation networks. This presentation will discuss the establishment of an institutional unit entitled ‘Human Development Unit’ (HDU) in a European start-up university. The activities of the HDU are envisioned as drivers for innovation that would enable the university as a whole to maintain its position in a fast-changing world and be ready to face adaptive challenges. In addition, the HDU provides its students, staff, and faculty with opportunities to advance their academic and professional development through engagement in programs that align with institutional values. It also serves as a connector with the broader community. The presentation will highlight the functions of three centers which the unit will coordinate namely, the Student Development Center (SDC), the Faculty & Staff Development Center (FSDC) and the Continuing Education Center (CEC). The presentation aligns with the aim of the conference as it welcomes presentations to discuss innovations and challenges encountered in HE. Particularly, this presentation seeks to discuss the establishment of an innovative unit at a start-up university which will contribute to creating an institutional culture shaped by the value of academic excellence for students as well as for staff, shaping and defining the functions and activities of the unit. The establishment of the proposed unit is crucial in a start-up university both to differentiate from other competitors but also to sustain its presence given the pressures in a neoliberal HE context.

Keywords: academic excellence, globalization, human development unit, neoliberalism

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Authors: Truong H. Le, Ngoc M. To, Quang N. Tran, Luu T. Cao, Chi V. Le

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Introduction: In Vietnam, the current monitoring and treatment for ordinary diabetic patient mostly based on glucose monitoring with HbA1c test for every three months (recommended goal is HbA1c < 6.5%~7%). For diabetes in pregnant women or Gestational diabetes mellitus (GDM), glycemic control until the time of delivery is extremly important because it could reduce significantly medical implications for both the mother and the child. Besides, GDM requires continuos glucose monitoring at least every two weeks and therefore an alternative marker of glycemia for short-term control is considering a potential tool for the healthcare providers. There are published studies have indicated that the glycosylated serum protein is a better indicator than glycosylated hemoglobin in GDM monitoring. Based on the actual practice in Vietnam, this study was designed to evaluate the role of serum fructosamine as a monitoring tool in GDM treament and its correlations with fasting blood glucose (G0), 2-hour postprandial glucose (G2) and glycosylated hemoglobin (HbA1c). Methods: A cohort study on pregnant women diagnosed with GDM by the 75-gram oralglucose tolerance test was conducted at Endocrinology Department, Cho Ray hospital, Vietnam from June 2014 to March 2015. Cho Ray hospital is the final destination for GDM patient in the southern of Vietnam, the study population has many sources from other pronvinces and therefore researchers belive that this demographic characteristic can help to provide the study result as a reflection for the whole area. In this study, diabetic patients received a continuos glucose monitoring method which consists of bi-weekly on-site visit every 2 weeks with glycosylated serum protein test, fasting blood glucose test and 2-hour postprandial glucose test; HbA1c test for every 3 months; and nutritious consultance for daily diet program. The subjects still received routine treatment at the hospital, with tight follow-up from their healthcare providers. Researchers recorded bi-weekly health conditions, serum fructosamine level and delivery outcome from the pregnant women, using Stata 13 programme for the analysis. Results: A total of 500 pregnant women was enrolled and follow-up in this study. Serum fructosamine level was found to have a light correlation with G0 ( r=0.3458, p < 0.001) and HbA1c ( r=0.3544, p < 0.001), and moderately correlated with G2 ( r=0.4379, p < 0.001). During study timeline, the delivery outcome of 287 women were recorded with the average age of 38.5 ± 1.5 weeks, 9% of them have macrosomia, 2.8% have premature birth before week 35th and 9.8% have premature birth before week 37th; 64.8% of cesarean section and none of them have perinatal or neonatal mortality. The study provides a reference interval of serum fructosamine for GDM patient was 112.9 ± 20.7 μmol/dL. Conclusion: The present results suggests that serum fructosamine is as effective as HbA1c as a reflection of blood glucose control in GDM patient, with a positive result in delivery outcome (0% perinatal or neonatal mortality). The reference value of serum fructosamine measurement provided a potential monitoring utility in GDM treatment for hospitals in Vietnam. Healthcare providers in Cho Ray hospital is considering to conduct more studies to test this reference as a target value in their GDM treatment and monitoring.

Keywords: gestational diabetes mellitus, monitoring tool, serum fructosamine, Vietnam

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Authors: Josie Gardner

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The overall intention of this research is to reimagine peacebuilding in both in theory and practical application in light of the shortcomings and unsustainability of the current peacebuilding paradigm. These limitations are identified here as an overly rational-material approach to peacebuilding that neglects the inner dimension of peace for a fragmented rather than holistic model, and that espouses a conflict and violence-centric approach to peacebuilding. In counter, this presentation is purposed to investigate the dynamics of inner and outer peace as a holistic, complex system towards ‘inner-outer’ peacebuilding. This paper draws from primary research in the protracted conflict context of north-western India (Jammu, Kashmir & Ladakh) as a case study. This presentation has two central aims. First, to introduce the process of inner (psycho-spiritual) peacebuilding, which has thus far been neglected by mainstream and orthodox literature. Second, to examine why inner peacebuilding is essential for realising sustainable peace on a broader scale as outer (socio-political) peace and to better understand how the inner and outer dynamics of peace relate and affect one another. To these ends, Josephine (the researcher/author/presenter) partnered with Yakjah Reconciliation and Development Network to implement a series of action-oriented workshops and retreats centred around healing, reconciliation, leadership, and personal development for the dual purpose of collaboratively generating data, theory, and insights, as well as providing the youth leaders with an experiential, transformative experience. The research team created and used a novel methodological approach called Mapping Ritual Ecologies, which draws from Participatory Action Research and Digital Ethnography to form a collaborative research model with a group of 20 youth co-researchers who are emerging youth peace leaders in Kashmir, Jammu, and Ladakh. This research found significant intra- and inter-personal shifts towards an experience of inner peace through inner peacebuilding activities. Moreover, this process of inner peacebuilding affected their families and communities through interpersonal healing and peace leadership in an inside-out process of change. These insights have generated rich insights and have supported emerging theories about the dynamics between inner and outer peace, power, justice, and collective healing. This presentation argues that the largely neglected dimension of inner (psycho-spiritual) peacebuilding is imperative for broader socio-political (outer) change. Changing structures of oppression, injustice, and violence—i.e. structures of separation—requires individual, interpersonal, and collective healing. While this presentation primarily examines and advocates for inside-out peacebuilding and social justice, it will also touch upon the effect of systems of separation on the inner condition and human experience. This research reimagines peacebuilding as a holistic inner-outer approach. This offers an alternative path forward those weaves together self-actualisation and social justice. While contextualised within north-western India with a small case study population, the findings speak also to other conflict contexts as well as our global peacebuilding and social justice milieu.

Keywords: holistic, inner peacebuilding, psycho-spiritual, systems youth

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Authors: Aathira Peedikaparambil Somasundaran

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The beginning of the 20th century marked the perios when a new generation of Lebanese radicals sowed the seeds for the second phase of Levant literary modernism, situated in the Levant. Beirut, during this era popularly fit every radical writer’s criterion owing to its weakened censorship and political control, despite the absence of a protective womb for the development of literary modernism, caused by the natively prevalent political unsettlement. The third stage of literary modernization, in which scholars used Western-inspired critical techniques to better understand their own cultures, coincides with the time period examined in this paper, which involved the international-inspired critical analysis of native cultural stimulants, which raised questions among Arab freethinking intellectuals. Locals who ventured outside recognised the difference between the West's progress and their own nations' stagnation. The awareness of such ‘gap of success’ aroused an ambition from journalists, authors, and proletarian revolutionaries who had studied in Europe, and finally developed enlightened ideas. Some Middle Eastern authors and artists only adopted current social and political frameworks after discovering western modernity. After learning about the upheavals that were happening in the West, these thinkers aspired to bring about equally broad drastic developments in their own country's social, political, and cultural milieu. These occurrences illustrate the increased power of migration to alter the cultural and literary scene in the Levant. The paper intends to discuss the different effects of migration that contributed to Levant literary modernism. The exploration of these factors as causes begins with addressing the politically influenced activism, that has always been a relevant part of Beirut, and then diving into the psychological effects of migration in the individuals of the society, which might have induced an accommodability to alien thoughts and ideas over time, as a coping mechanism. Nature or environmental stimuli, a common trigger for any creative output, often having the highest influence during travel will be identified and analysed to inspect the extent of its impact on the exchange of ideas that resulted in Levant modernism. The efficiency of both the stimulating component of travel and the diaspora of the indigenous, a by-product of travel in catalysing modernism in the Levant has to be proven in order to understand how migration indirectly affected the transmission and adoption of ideas in Levant literature. The paper will revisit the events revolving around these key players and platforms like Shir, to understand how the Lebanese literature, tied down in poetry drastically mutated under the leadership of Adonis, Yusuf et Khal, and other pioneers of Levant literary modernism. The conclision will identify the triggers that helped authors overcome personal and geographical barriers to unite the West and the Levant, and investigate the extent to which the bi-directional migration prompted a transformation in the local poetry. Consequently, the paper aims to shed light into the unique factor that provoked the shift in the literary scene of Twentieth century in the Middle East.

Keywords: literature, modernism, Middle East, levant, Beirut

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Authors: Cristina Maria Mendoza Sanchez, Maria Angeles Navarro Perán

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Introduction: Nursing as a profession, from its initial formation and after its development in practice, has been built and identified mainly from its technical competence and professionalization within the positivist approach of the XIX century that provides a conception of the disease built on the basis of to the biomedical paradigm, where the care provided is more focused on the physiological processes and the disease than on the suffering person understood as a whole. The main issue that is in need of study here is a review of the nursing profession's history to get to know how the nursing profession was before the XIX century. It is unclear if there were organizations or people with knowledge about looking after others or if many people survived by chance. The holistic care, in which the appearance of the disease directly affects all its dimensions: physical, emotional, cognitive, social and spiritual. It is not a concept from the 21st century. It is common practice, most probably since established life in this world, with the final purpose of covering all these perspectives through quality care. Objective: In this paper, we describe and analyze the history of education in nursing learning in terms of reviewing and analysing theoretical foundations of clinical teaching and learning in nursing, with the final purpose of determining and describing the development of the nursing profession along the history. Method: We have done a descriptive systematic review study, doing a systematically searched of manuscripts and articles in the following health science databases: Pubmed, Scopus, Web of Science, Temperamentvm and CINAHL. The selection of articles has been made according to PRISMA criteria, doing a critical reading of the full text using the CASPe method. A compliment to this, we have read a range of historical and contemporary sources to support the review, such as manuals of Florence Nightingale and John of God as primary manuscripts to establish the origin of modern nursing and her professionalization. We have considered and applied ethical considerations of data processing. Results: After applying inclusion and exclusion criteria in our search, in Pubmed, Scopus, Web of Science, Temperamentvm and CINAHL, we have obtained 51 research articles. We have analyzed them in such a way that we have distinguished them by year of publication and the type of study. With the articles obtained, we can see the importance of our background as a profession before modern times in public health and as a review of our past to face challenges in the near future. Discussion: The important influence of key figures other than Nightingale has been overlooked and it emerges that nursing management and development of the professional body has a longer and more complex history than is generally accepted. Conclusions: There is a paucity of studies on the subject of the review to be able to extract very precise evidence and recommendations about nursing before modern times. But even so, as more representative data, an increase in research about nursing history has been observed. In light of the aspects analyzed, the need for new research in the history of nursing emerges from this perspective; in order to germinate studies of the historical construction of care before the XIX century and theories created then. We can assure that pieces of knowledge and ways of care were taught before the XIX century, but they were not called theories, as these concepts were created in modern times.

Keywords: nursing history, nursing theory, Saint John of God, Florence Nightingale, learning, nursing education

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Authors: Jonas De Kerf, Rein De Cooman, Sara De Gieter

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For many decades, scholars have aimed to understand how work can become more meaningful by maximizing both potential and enhancing feelings of satisfaction. One of the largest contributions towards such positive psychology was made with the introduction of the concept of ‘flow,’ which refers to a condition in which people feel intense engagement and effortless action. Since then, valuable research on work-related flow has indicated that this state of mind is related to positive outcomes for both organizations (e.g., social, supportive climates) and workers (e.g., job satisfaction). Yet, scholars still do not fully comprehend how such deep involvement at work is obtained, given the notion that flow is considered a short-term, complex, and dynamic experience. Most research neglects that people who experience flow ought to be optimally challenged so that intense concentration is required. Because attention is at the core of this enjoyable state of mind, this study aims to comprehend how elements that affect workers’ cognitive functioning impact flow at work. Research on cognitive performance suggests that working on mentally demanding tasks (e.g., information processing tasks) requires workers to concentrate deeply, as a result leading to flow experiences. Based on social facilitation theory, working on such tasks in an isolated environment eases concentration. Prior research has indicated that working at home (instead of working at the office) or in a closed office (rather than in an open-plan office) impacts employees’ overall functioning in terms of concentration and productivity. Consequently, we advance such knowledge and propose an interaction by combining cognitive task characteristics and work environments among part-time teleworkers. Hence, we not only aim to shed light on the relation between cognitive tasks and flow but also provide empirical evidence that workers performing such tasks achieve the highest states of flow while working either at home or in closed offices. In July 2022, an experience-sampling study will be conducted that uses a semi-random signal schedule to understand how task and environment predictors together impact part-time teleworkers’ flow. More precisely, about 150 knowledge workers will fill in multiple surveys a day for two consecutive workweeks to report their flow experiences, cognitive tasks, and work environments. Preliminary results from a pilot study indicate that on a between level, tasks high in information processing go along with high self-reported fluent productivity (i.e., making progress). As expected, evidence was found for higher fluency in productivity for workers performing information processing tasks both at home and in a closed office, compared to those performing the same tasks at the office or in open-plan offices. This study expands the current knowledge on work-related flow by looking at a task and environmental predictors that enable workers to obtain such a peak state. While doing so, our findings suggest that practitioners should strive for ideal alignments between tasks and work locations to work with both deep involvement and gratification.

Keywords: cognitive work, office lay-out, work location, work-related flow

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Authors: Tibor Ajtai, Máté Pintér, Noémi Utry, Gergely Kiss-Albert, Andrea Palágyi, László Manczinger, Csaba Vágvölgyi, Gábor Szabó, Zoltán Bozóki

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According to the best knowledge of the authors, here we experimentally demonstrate first, a quantified correlation between the real-time measured optical feature of the ambient and the off-line measured toxicity data. Finally, using these correlations we are presenting a novel methodology for real time characterisation of ambient toxicity based on the multi wavelength aerosol phase photoacoustic measurement. Ambient carbonaceous particulate matter is one of the most intensively studied atmospheric constituent in climate science nowadays. Beyond their climatic impact, atmospheric soot also plays an important role as an air pollutant that harms human health. Moreover, according to the latest scientific assessments ambient soot is the second most important anthropogenic emission source, while in health aspect its being one of the most harmful atmospheric constituents as well. Despite of its importance, generally accepted standard methodology for the quantitative determination of ambient toxicology is not available yet. Dominantly, ambient toxicology measurement is based on the posterior analysis of filter accumulated aerosol with limited time resolution. Most of the toxicological studies are based on operational definitions using different measurement protocols therefore the comprehensive analysis of the existing data set is really limited in many cases. The situation is further complicated by the fact that even during its relatively short residence time the physicochemical features of the aerosol can be masked significantly by the actual ambient factors. Therefore, decreasing the time resolution of the existing methodology and developing real-time methodology for air quality monitoring are really actual issues in the air pollution research. During the last decades many experimental studies have verified that there is a relation between the chemical composition and the absorption feature quantified by Absorption Angström Exponent (AAE) of the carbonaceous particulate matter. Although the scientific community are in the common platform that the PhotoAcoustic Spectroscopy (PAS) is the only methodology that can measure the light absorption by aerosol with accurate and reliable way so far, the multi-wavelength PAS which are able to selectively characterise the wavelength dependency of absorption has become only available in the last decade. In this study, the first results of the intensive measurement campaign focusing the physicochemical and toxicological characterisation of ambient particulate matter are presented. Here we demonstrate the complete microphysical characterisation of winter time urban ambient including optical absorption and scattering as well as size distribution using our recently developed state of the art multi-wavelength photoacoustic instrument (4λ-PAS), integrating nephelometer (Aurora 3000) as well as single mobility particle sizer and optical particle counter (SMPS+C). Beyond this on-line characterisation of the ambient, we also demonstrate the results of the eco-, cyto- and genotoxicity measurements of ambient aerosol based on the posterior analysis of filter accumulated aerosol with 6h time resolution. We demonstrate a diurnal variation of toxicities and AAE data deduced directly from the multi-wavelength absorption measurement results.

Keywords: photoacoustic spectroscopy, absorption Angström exponent, toxicity, Ames-test

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Authors: Husham Bayazed

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Purpose of Presentation: Obesity and overweight are among the biggest health challenges of the 21st century, according to the WHO. Obviously, obese individuals suffer different courses of disease – from infections and allergies to cancer- and even respond differently to some treatment options. Of note, obesity often seems to predispose and triggers several secondary diseases such as diabetes, arteriosclerosis, or heart attacks. Since decades it seems that immunological signals gear inflammatory processes among obese individuals with the aforementioned conditions. This review aims to shed light how obesity sparks or rewire the immune system and predisposes to such unpleasant health outcomes. Moreover, lessons from the Covid-19 pandemic ascertain that people living with pre-existing conditions such as obesity can develop severe acute respiratory syndrome (SARS), which needs to be elucidated how obesity and its adjuvant inflammatory process distortion contribute to enhancing severe COVID-19 consequences. Recent Findings: In recent clinical studies, obesity was linked to alter and sparks the immune system in different ways. Adipose tissue (AT) is considered as a secondary immune organ, which is a reservoir of tissue-resident of different immune cells with mediator release, making it a secondary immune organ. Adipocytes per se secrete several pro-inflammatory cytokines (IL-6, IL-4, MCP-1, and TNF-α ) involved in activation of macrophages resulting in chronic low-grade inflammation. The correlation between obesity and T cells dysregulation is pivotal in rewiring the immune system. Of note, autophagy occurrence in adipose tissues further rewire the immune system due to flush and outburst of leptin and adiponectin, which are cytokines and influencing pro-inflammatory immune functions. These immune alterations among obese individuals are collectively incriminated in triggering several metabolic disorders and playing role in increasing cancers incidence and susceptibility to different infections. During COVID-19 pandemic, it was verified that patients with pre-existing obesity being at greater risk of suffering severe and fatal clinical outcomes. Beside obese people suffer from increased airway resistance and reduced lung volume, ACE2 expression in adipose tissue seems to be high and even higher than that in lungs, which spike infection incidence. In essence, obesity with pre-existence of pro-inflammatory cytokines such as LI-6 is a risk factor for cytokine storm and coagulopathy among COVID-19 patients. Summary: It is well documented that obesity is associated with chronic systemic low-grade inflammation, which sparks and alter different pillars of the immune system and triggers different metabolic disorders, and increases susceptibility of infections and cancer incidence. The pre-existing chronic inflammation in obese patients with the augmented inflammatory response against the viral infection seems to increase the susceptibility of these patients to developing severe COVID-19. Although the new weight loss drugs and bariatric surgery are considered as breakthrough news for obesity treatment, but preventing is easier than treating it once it has taken hold. However, obesity and immune system link new insights dispute the role of immunotherapy and regulating immune cells treating diet-induced obesity.

Keywords: immunity, metabolic disorders, cancer, COVID-19

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Authors: Judith Sue Hwa Joo

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Guanyin (Avalokiteśvara in Sanskrit), the Bodhisattva of Mercy and Compassion, is the most widely worshipped Buddhist Divinity in Chinese societies and is also believed by more than half of Asian populations across various countries. The most overwhelming reason for the popularity of Guanyin in Chinese societies is, according to the Lotus Sutra, that Guanyin would apperceive voices of those suffering from immense afflictions and troubles, and liberate them upon crying for his/her holy name with wholeheartedness. Its pervasive social influence has spanned more than two thousand years and is still deeply affecting the lives of most Chinese people. This study aimed to investigate whether Guanyin Worship has evolved and changed in modern Chinese societies across the Taiwan Strait. Taiwan and China, albeit having the same language and culture, have been territorially divided and governed by two different political regimes for over 70 years. It would be scientifically intriguing to unveil any substantial changes in religious behaviors in the context of Guanyin Worship. A comprehensive anonymous questionnaire survey in Chinese communities was conducted from October 2017 to May 2019 across various countries, mostly in China, Taiwan, and Hong Kong areas. Since the religious survey is officially prohibited in China, the study was difficult and could only be exercised by means of snowball sampling. Demographic data (age, sex, education, religious belief) were registered and Guanyin’s salvation functions under various confronting situations were investigated. Psychological dimensions of religious belief in Guanyin were probed in terms of the worship experience, the willingness of veneration, and egoistic or altruistic ideations. A literature review on documented functional attributes was carried out in parallel for comparison analyses with traditional roles. Effective 1123 out of 1139 samples were obtained. Statistical analysis revealed that Guanyin Worship is still commonly practiced and deeply rooted in the hearts of all Chinese people regardless of gender, age, education, and residential area, even though they may not enshrine Guanyin at home nowadays. The conventional roles of Guanyin Bodhisattva are still valid and best satisfy the real interests of lifestyles in modern times. When comparing the traditional Buddhist Sutra and the documented literature, the divine power of modern Guanyin has notably empowered to recover, protect and transform fetal and infant spirits due to the sexual liberation, increased abortion rate, gender awakening and enhanced female autonomy in the reproductive decision. However, the One-Child policy may have critically impacted the trajectory of Guanyin Worship so that people in China prevail over those in Taiwan praying for aborted lives or premature deaths. Furthermore, particularly in Hong Kong and Macao, Guanyin not only serves as the sea guardian for the fishermen but also additional services a new function as the God of Wealth. The divine powers and salvation functions of Guanyin are indeed evolving and expanding to comply with the modern psychosocial, cultural and societal needs. This study sheds light on the modernization process of the two-thousand-year-old Guanyin Worship of contemporary Chinese societies.

Keywords: Buddhism, Guanyin, religious behavior, salvation function

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Authors: Olagunju John Olusesan-Remi

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The study area Ijero-Ekiti falls within the Ilesha-Ekiti Schist belt, originating from the long year of the Pan-Africa orogenic events and various cataclysmic tectonic activities in history. Ijero-Ekiti is situated within latitude 7 degree 45N and 7 Degree 55N. Ijero Ekiti is bordered between the Dahomean Basin and the southern Bida/Benue basin on the Geological map of Nigeria. This research work centers on majorly on investigating the chemical composition and as well as the mineralogical distribution of the various mineral-bearing rocks that composed the study area. This work is essentially carried out with a view to assessing and at the same time ascertaining the economic potentials and or the industrial significance of the area to Ekiti-south western region and the Nigeria nation as a whole. The mineralogical distribution pattern is of particular interest to us in this study. In this regard essential focus is put on the mostly the economic gemstones distributions within the various mineral bearing rocks in the zone, some of which includes the tourmaline formation, cassiterite deposit, tin-ore, tantalum columbite, smoky quartz, amethyst, polychrome and emerald variety beryl among others as they occurred within the older granite of the Precambrian rocks. To this end, samples of the major rock types were taken from various locations within the study area for detail scientific analysis as follows: The Igemo pegmatite of Ijero west, the epidiorite of Idaho, the biotitic hornblende gneiss of Ikoro-Ijero north and the beryl crystalline rock types to mention a few. The slides of the each rock from the aforementioned zones were later prepared and viewed under a cross Nichol petro graphic microscope with a particular focus on the light reflection ability of the constituent minerals in each rock samples. The results from the physical analysis viewed from the colour had it that the pegmatite samples ranges from pure milky white to fairly pinkish coloration. Other physical properties investigated include the streak, luster, form, specific gravity, cleavage/fracture pattern etc. The optical examination carried out centers on the refractive indices and pleochroism of the minerals present while the chemical analysis reveals from the tourmaline samples a differing correlation coefficient of the various oxides in each samples collected through which the mineral presence was established. In conclusion, it was inferred that the various minerals outlined above were in reasonable quantity within the Ijero area. With the above discoveries, therefore, we strongly recommend a detailed scientific investigation to be carried out such that will lead to a comprehensive mining of the area. Above all, it is our conclusion that a comprehensive mineralogical exploitation of this area will not only boost the socio-economic potential of the area but at the same time will go a long way contributing immensely to the socio-economic growth and development of the Nation-Nigeria at large.

Keywords: Ijero Ekiti, Southwestern Nigeria, economic minerals, pegmatite of the pan African origin, cataclastic tectonic activities, Ilesha Schistbelt, precambrian formations

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Authors: Birgit A. A. Solem, Kristin Bentsen

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Scholarly attention in entrepreneurship is currently directed towards understanding entrepreneurial venture creation as a process -the journey of new economic activities from nonexistence to existence often studied through flow- or network models. To complement existing research on entrepreneurial venture creation with more interactivity-based research of organized activities, this study examines two pop-up stores as anchor events involving on-site activities of fifteen participating entrepreneurs launching their new ventures. The pop-up stores were arranged in two middle-sized Norwegian cities and contained different brand stores that brought together actors of sub-networks and communities executing venture creation activities. The pop-up stores became on-site arenas for the entrepreneurs to create, maintain, and rejuvenate their networks, at the same time as becoming venues for temporal coordination of activities involving existing and potential customers in their venture creation. In this work, we apply a conceptual framework based on frequently addressed dilemmas within entrepreneurship theory (discovery/creation, causation/effectuation) to further shed light on the broad aspect of on-site anchor event activities and their venture creation outcomes. The dilemma-based concepts are applied as an analytic toolkit to pursue answers regarding the nature of anchor event activities typically found within entrepreneurial venture creation and how these anchor event activities affect entrepreneurial venture creation outcomes. Our study combines researcher participation with 200 hours of observation and twenty in-depth interviews. Data analysis followed established guidelines for hermeneutic analysis and was intimately intertwined with ongoing data collection. Data was coded and categorized in NVivo 12 software, and iterated several times as patterns were steadily developing. Our findings suggest that core anchor event activities typically found within entrepreneurial venture creation are; a concept- and product experimentation with visitors, arrangements to socialize (evening specials, auctions, and exhibitions), store-in-store concepts, arranged meeting places for peers and close connection with municipality and property owners. Further, this work points to four main entrepreneurial venture creation outcomes derived from the core anchor event activities; (1) venture attention, (2) venture idea-realization, (3) venture collaboration, and (4) venture extension. Our findings show that, depending on which anchor event activities are applied, the outcomes vary. Theoretically, this study offers two main implications. First, anchor event activities are both discovered and created, following the logic of causation, at the same time as being experimental, based on “learning by doing” principles of effectuation during the execution. Second, our research enriches prior studies on venture creation as a process. In this work, entrepreneurial venture creation activities and outcomes are understood through pop-up stores as on-site anchor event arenas, particularly suitable for interactivity-based research requested by the entrepreneurship field. This study also reveals important managerial implications, such as that entrepreneurs should allow themselves to find creative physical venture creation arenas (e.g., pop-up stores, showrooms), as well as collaborate with partners when discovering and creating concepts and activities based on new ideas. In this way, they allow themselves to both strategically plan for- and continually experiment with their venture.

Keywords: anchor event, interactivity-based research, pop-up store, entrepreneurial venture creation

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Authors: Tamam Albelwi, Robert Rogers, Hans-Peter Kubis

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Background: Exercise is widely acknowledged as a highly important health behavior, which reduces risks related to lifestyle diseases like type 2 diabetes, cardiovascular disease. However, exercise adherence is low in high-risk groups and sedentary lifestyle is more the norm than the exception. Expressed reasons for exercise participation are often based on delayed outcomes related to health threats and benefits but also enjoyment. Whether exercise is perceived as rewarding is well established in animal literature but the evidence is sparse in humans. Additionally, the question how stable any reward is perceived with time delays is an important question influencing decision-making (in favor or against a behavior). For the modality exercise, this has not been examined before. We, therefore, investigated the discounting of pre-established self-selected exercise compared with established rewards of food and money with a computer-based discounting paradigm. We hypothesized that exercise will be discounted like an established reward (food and money); however, we expect that the discounting rate is similar to a consumable reward like food. Additionally, we expected that individuals’ characteristics like preferred intensity, physical activity and body characteristics are associated with discount rates. Methods: 71 participants took part in four sessions. The sessions were designed to let participants select their preferred exercise intensity on a treadmill. Participants were asked to adjust their speed for optimizing pleasantness over an exercise period of up to 30 minutes, heart rate and pleasantness rating was measured. In further sessions, the established exercise intensity was modified and tested on perceptual validity. In the last exercise session rates of perceived exertion was measured on the preferred intensity level. Furthermore, participants filled in questionnaires related to physical activity, mood, craving, and impulsivity and answered choice questions on a bespoke computer task to establish discounting rates of their preferred exercise (kex), their favorite food (kfood) and a value-matching amount of money (kmoney). Results: Participants self-selected preferred speed was 5.5±2.24 km/h, at a heart rate of 120.7±23.5, and perceived exertion scale of 10.13±2.06. This shows that participants preferred a light exercise intensity with low to moderate cardiovascular strain based on perceived pleasantness. Computer assessment of discounting rates revealed that exercise was quickly discounted like a consumable reward, no significant difference between kfood and kex (kfood =0.322±0.263; kex=0.223±0.203). However, kmoney (kmoney=0.080±0.02) was significantly lower than the rates of exercise and food. Moreover, significant associations were found between preferred speed and kex (r=-0.302) and between physical activity levels and preferred speed (r=0.324). Outcomes show that participants perceived and discounted self-selected exercise like an established reward (food and money) but was discounted more like consumable rewards. Moreover, exercise discounting was quicker in individuals who preferred lower speeds, being less physically active. This may show that in a choice conflict between exercise and food the delay of exercise (because of distance) might disadvantage exercise as the chosen behavior particular in sedentary people. Conclusion: exercise can be perceived as a reward and is discounted quickly in time like food. Pleasant exercise experience is connected to low to moderate cardiovascular and perceptual strain.

Keywords: delay discounting, exercise, temporal discounting, time perspective

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Authors: Jara Kaye S. Villanueva, M. Rosario Concepcion O. Ang

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For the past few years, Philippines has depended most of its energy source on oil, coal, and fossil fuel. According to the Department of Energy (DOE), the dominance of coal in the energy mix will continue until the year 2020. The expanding energy needs in the country have led to increasing efforts to promote and develop renewable energy. This research is a part of the government initiative in preparation for renewable energy development and expansion in the country. The Philippine Renewable Energy Resource Mapping from Light Detection and Ranging (LiDAR) Surveys is a three-year government project which aims to assess and quantify the renewable energy potential of the country and to put them into usable maps. This study focuses on the site suitability analysis of the four renewable energy sources – biomass (coconut, corn, rice, and sugarcane), hydro, solar, and wind energy. The site assessment is a key component in determining and assessing the most suitable locations for the construction of renewable energy power plants. This method maximizes the use of both the technical methods in resource assessment, as well as taking into account the environmental, social, and accessibility aspect in identifying potential sites by utilizing and integrating two different methods: the Multi-Criteria Decision Analysis (MCDA) method and Geographic Information System (GIS) tools. For the MCDA, Analytical Hierarchy Processing (AHP) is employed to determine the parameters needed for the suitability analysis. To structure these site suitability parameters, various experts from different fields were consulted – scientists, policy makers, environmentalists, and industrialists. The need to have a well-represented group of people to consult with is relevant to avoid bias in the output parameter of hierarchy levels and weight matrices. AHP pairwise matrix computation is utilized to derive weights per level out of the expert’s gathered feedback. Whereas from the threshold values derived from related literature, international studies, and government laws, the output values were then consulted with energy specialists from the DOE. Geospatial analysis using GIS tools translate this decision support outputs into visual maps. Particularly, this study uses Euclidean distance to compute for the distance values of each parameter, Fuzzy Membership algorithm which normalizes the output from the Euclidean Distance, and the Weighted Overlay tool for the aggregation of the layers. Using the Natural Breaks algorithm, the suitability ratings of each of the map are classified into 5 discrete categories of suitability index: (1) not suitable (2) least suitable, (3) suitable, (4) moderately suitable, and (5) highly suitable. In this method, the classes are grouped based on the best groups similar values wherein each subdivision are set from the rest based on the big difference in boundary values. Results show that in the entire Philippine area of responsibility, biomass has the highest suitability rating with rice as the most suitable at 75.76% suitability percentage, whereas wind has the least suitability percentage with score 10.28%. Solar and Hydro fall in the middle of the two, with suitability values 28.77% and 21.27%.

Keywords: site suitability, biomass energy, hydro energy, solar energy, wind energy, GIS

Procedia PDF Downloads 149

Authors: Xu Qian

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This abstract examines the concept of resilience in adolescents from both adolescent medicine and child psychology perspectives. It discusses the role of healthcare providers in fostering resilience among adolescents, encompassing physical, psychological, and social aspects. The paper highlights evidence-based interventions and practical strategies for promoting resilience in this population. Introduction: Resilience plays a crucial role in the healthy development of adolescents, enabling them to navigate through the challenges of this transitional period. This abstract explores the concept of resilience from the perspectives of adolescent medicine and child psychology, shedding light on the collective efforts of healthcare providers in fostering resilience. By integrating the principles and practices of these two disciplines, this abstract emphasizes the multidimensional nature of resilience and its significance in the overall well-being of adolescents. Methods: A comprehensive literature review was conducted, encompassing research articles, empirical studies, and expert opinions from both adolescent medicine and child psychology fields. The search included databases such as PubMed, PsycINFO, and Google Scholar, focusing on publications from the past decade. The review aimed to identify evidence-based interventions and practical strategies employed by healthcare providers to promote resilience among adolescents. Results: The review revealed several key findings regarding the promotion of resilience in adolescents. Firstly, resilience is a dynamic process influenced by individual characteristics, environmental factors, and the interaction between the two. Secondly, healthcare providers play a critical role in fostering resilience by addressing the physical, psychological, and social needs of adolescents. This entails comprehensive healthcare services that integrate medical care, mental health support, and social interventions. Thirdly, evidence-based interventions such as cognitive-behavioral therapy, social skills training, and positive youth development programs have shown promising outcomes in enhancing resilience. Discussion: The integration of adolescent medicine and child psychology perspectives provides a comprehensive framework for promoting resilience in adolescents. By acknowledging the interplay between physical health, psychological well-being, and social functioning, healthcare providers can tailor interventions to address the specific needs and challenges faced by adolescents. Collaborative efforts between medical professionals, psychologists, educators, and families are vital in creating a supportive environment that fosters resilience. Additionally, the findings highlight the importance of early identification and intervention, emphasizing the need for routine screening and assessment to identify adolescents at risk and provide timely support. Conclusion: Promoting resilience in adolescents requires a holistic approach that integrates adolescent medicine and child psychology perspectives. By recognizing the multifaceted nature of resilience, healthcare providers can implement evidence-based interventions and practical strategies to enhance the well-being of adolescents. The collaboration between healthcare professionals from different disciplines, alongside the involvement of families and communities, is crucial for creating a resilient support system. By investing in the promotion of resilience during adolescence, we can empower young individuals to overcome adversity and thrive in their journey toward adulthood.

Keywords: psychology, clinical psychology, child psychology, adolescent psychology, adolescent

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Authors: Julian Iliev

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The recent release of The Matrix Resurrections persuaded many film scholars that The Matrix trilogy had lost its appeal and its concepts were largely outdated. This study examines the human pods and growing fields in the trilogy. Their functionality is compared to Michel Foucault’s concept of docile bodies: linking fictional and contemporary worlds. This paradigm is scrutinized through surveillance literature. The analogy brings to light common elements of hidden surveillance practices in technologies. The comparison illustrates the effects of body manipulation portrayed in the movies and their relevance with contemporary surveillance practices. Many scholars have utilized a close reading methodology in film studies (J.Bizzocchi, J.Tanenbaum, P.Larsen, S. Herbrechter, and Deacon et al.). The use of a particular lens through which media text is examined is an indispensable factor that needs to be incorporated into the methodology. The study spotlights both scenes from the trilogy depicting the human pods and growing fields. The functionality of the pods and the fields compare directly with Foucault’s concept of docile bodies. By utilizing Foucault’s study as a lens, the research will unearth hidden components and insights into the films. Foucault recognizes three disciplines that produce docile bodies: 1) manipulation and the interchangeability of individual bodies, 2) elimination of unnecessary movements and management of time, and 3) command system guaranteeing constant supervision and continuity protection. These disciplines can be found in the pods and growing fields. Each body occupies a single pod aiding easier manipulation and fast interchangeability. The movement of the bodies in the pods is reduced to the absolute minimum. Thus, the body is transformed into the ultimate object of control – minimum movement correlates to maximum energy generation. Supervision is exercised by wiring the body with numerous types of cables. This ultimate supervision of body activity reduces the body’s purpose to mere functioning. If a body does not function as an energy source, then it’s unplugged, ejected, and liquefied. The command system secures the constant supervision and continuity of the process. To Foucault, the disciplines are distinctly different from slavery because they stop short of a total takeover of the bodies. This is a clear difference from the slave system implemented in the films. Even though their system might lack sophistication, it makes up for it in the elevation of functionality. Further, surveillance literature illustrates the connection between the generation of body energy in The Matrix trilogy to the generation of individual data in contemporary society. This study found that the three disciplines producing docile bodies were present in the portrayal of the pods and fields in The Matrix trilogy. The above comparison combined with surveillance literature yields insights into analogous processes and contemporary surveillance practices. Thus, the constant generation of energy in The Matrix trilogy can be equated to the consistent data generation in contemporary society. This essay shows the relevance of the body manipulation concept in the Matrix films with contemporary surveillance practices.

Keywords: docile bodies, film trilogies, matrix movies, michel foucault, privacy loss, surveillance

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Authors: Zografou Konstantina, Anagnostellis Konstantinos, Brokaki Marina, Kaltsouni Eleftheria, Dimaki Maria, Kati Vassiliki

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Body size is crucial to ecology, influencing everything from individual reproductive success to the dynamics of communities and ecosystems. Understanding how temperature affects variations in body size is vital for both theoretical and practical purposes, as changes in size can modify trophic interactions by altering predator-prey size ratios and changing the distribution and transfer of biomass, which ultimately impacts food web stability and ecosystem functioning. Notably, a decrease in body size is frequently mentioned as the third ‘universal’ response to climate warming, alongside shifts in distribution and changes in phenology. This trend is backed by ecological theories like the temperature-size rule (TSR) and Bergmann's rule, which have been observed in numerous species, indicating that many species are likely to shrink in size as temperatures rise. However, the thermal responses related to body size are still contradictory and further exploration is needed. To tackle this challenge, we developed the MEIOSIS project, aimed at providing valuable insights into the relationship between the body size of species, species’ traits, environmental factors and their response to climate change. We combined a digitized collection of butterflies from the Swiss Federal Institute of Technology in Zürich with our newly digitized butterfly collection from Goulandris Natural History Museum in Greece to analyze trends in time. For a total of 23868 images, the length of the right forewing was measured using ImageJ software. Each forewing was measured from the point at which the wing meets the thorax to the apex of the wing. The forewing length of museum specimens has been shown to have a strong correlation with wing surface area and has been utilized in prior studies as a proxy for overall body size. Temperature data corresponding to the years of collection were also incorporated into the datasets. A second dataset was generated when a custom computer vision tool was implemented for the automated morphological measuring of samples for the digitized collection in Zürich. Using the second dataset, we corrected manual measurements with ImageJ and a final dataset containing 31922 samples was used in analysis. Setting time as a smoother variable, species identity as a random factor and the length of right-wing size (as a proxy for body size) as the response variable, we ran a global model for a maximum period of 170 years (1840 – 2010). We also constructed individual models for each family (Pieridae, Lycaenidae, Hesperiidae, Nymphalidae, Papilionidae). All models confirmed our initial hypothesis and resulted in a decreasing trend of the wing length over the years. We expect that this first output can be provided as basic data for the next challenge, i.e., to identify the ecological traits that influence species' temperature-size responses, enabling us to predict the direction and intensity of a species' reaction to rising temperatures more accurately.

Keywords: butterflies, shrinking body size, museum specimens, climate change

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Authors: Luis Castiella, Mariano Rueda, Catalina Palacio

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The world’s rapid urbanisation represents an excellent opportunity to implement initiatives that are oriented towards a country’s general development. However, this phenomenon has created considerable pressure on current urban models, pushing them nearer to a crisis. As a result, several factors usually associated with underdevelopment have been steadily rising. Moreover, actions taken by public authorities have not been able to keep up with the speed of urbanisation, which has impeded them from meeting the demands of society, responding with reactionary policies instead of with coordinated, organised efforts. In contrast, the concept of a Smart City which emerged around two decades ago, in principle, represents a city that utilises innovative technologies to remedy the everyday issues of the citizen, empowering them with the newest available technology and information. This concept has come to adopt a wider meaning, including human and social capital, as well as productivity, economic growth, quality of life, environment and participative governance. These developments have also disrupted the management of institutions such as academia, which have become key in generating scientific advancements that can solve pressing problems, and in forming a specialised class that is able to follow up on these breakthroughs. In this light, the Ministry of Modernisation of the Argentinian Nation has created a model that is rooted in the concept of a ‘Smart City’. This effort considered all the dimensions that are at play in an urban environment, with careful monitoring of each sub-dimensions in order to establish the government’s priorities and improving the effectiveness of its operations. In an attempt to ameliorate the overall efficiency of the country’s economic and social development, these focused initiatives have also encouraged citizen participation and the cooperation of the private sector: replacing short-sighted policies with some that are coherent and organised. This process was developed gradually. The first stage consisted in building the model’s structure; the second, at applying the method created on specific case studies and verifying that the mechanisms used respected the desired technical and social aspects. Finally, the third stage consists in the repetition and subsequent comparison of this experiment in order to measure the effects on the ‘treatment group’ over time. The first trial was conducted on 717 municipalities and evaluated the dimension of Governance. Results showed that levels of governmental maturity varied sharply with relation to size: cities with less than 150.000 people had a strikingly lower level of governmental maturity than cities with more than 150.000 people. With the help of this analysis, some important trends and target population were made apparent, which enabled the public administration to focus its efforts and increase its probability of being successful. It also permitted to cut costs, time, and create a dynamic framework in tune with the population’s demands, improving quality of life with sustained efforts to develop social and economic conditions within the territorial structure.

Keywords: composite index, comprehensive model, smart cities, strategic framework

Procedia PDF Downloads 176

Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Sylvie Michel, Emmanuelle Gagnou, Joanne Hamet

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Researchers in the fields of AI and Robotics frequently encounter ethical dilemmas throughout their research endeavors. Various ethical challenges have been pinpointed in the existing literature, including biases and discriminatory outcomes, diffusion of responsibility, and a deficit in transparency within AI operations. This research aims to pinpoint these ethical quandaries faced by researchers and shed light on the mechanisms behind ethical decision-making in the research process. By synthesizing insights from existing literature and acknowledging prevalent shortcomings, such as overlooking the heterogeneous nature of decision-making, non-accumulative results, and a lack of consensus on numerous factors due to limited empirical research, the objective is to conceptualize and validate a model. This model will incorporate influences from individual perspectives and situational contexts, considering potential moderating factors in the ethical decision-making process. Qualitative analyses were conducted based on direct observation of an AI/Robotics research team focusing on collaborative robotics for several months. Subsequently, semi-structured interviews with 16 team members were conducted. The entire process took place during the first semester of 2023. Observations were analyzed using an analysis grid, and the interviews underwent thematic analysis using Nvivo software. An initial finding involves identifying the ethical challenges that AI/robotics researchers confront, underlining a disparity between practical applications and theoretical considerations regarding ethical dilemmas in the realm of AI. Notably, researchers in AI prioritize the publication and recognition of their work, sparking the genesis of these ethical inquiries. Furthermore, this article illustrated that researchers tend to embrace a consequentialist ethical framework concerning safety (for humans engaging with robots/AI), worker autonomy in relation to robots, and the societal implications of labor (can robots displace jobs?). A second significant contribution entails proposing a model for ethical decision-making within the AI/Robotics research sphere. The model proposed adopts a process-oriented approach, delineating various research stages (topic proposal, hypothesis formulation, experimentation, conclusion, and valorization). Across these stages and the ethical queries, they entail, a comprehensive four-point comprehension of ethical decision-making is presented: recognition of the moral quandary; moral judgment, signifying the decision-maker's aptitude to discern the morally righteous course of action; moral intention, reflecting the ability to prioritize moral values above others; and moral behavior, denoting the application of moral intention to the situation. Variables such as political inclinations ((anti)-capitalism, environmentalism, veganism) seem to wield significant influence. Moreover, age emerges as a noteworthy moderating factor. AI and robotics researchers are continually confronted with ethical dilemmas during their research endeavors, necessitating thoughtful decision-making. The contribution involves introducing a contextually tailored model, derived from meticulous observations and insightful interviews, enabling the identification of factors that shape ethical decision-making at different stages of the research process.

Keywords: ethical decision making, artificial intelligence, robotics, research

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Authors: Sun-Hee Lee, Amanda Kraley

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The “MeToo” movement is a social movement against sexual abuse and harassment. Though the hashtag went viral in 2017 following different cultural flashpoints in different countries, the initial response was quiet in South Korea. This radically changed in January 2018, when a high-ranking senior prosecutor, Seo Ji-hyun, gave a televised interview discussing being sexually assaulted by a colleague. Acknowledging public anger, particularly among women, on the long-existing problems of sexual harassment and abuse, the South Korean media have focused on several high-profile cases. Analyzing the media representation of these cases is a window into the evolving South Korean discourse around “MeToo.” This study presents a linguistic analysis of “MeToo” discourse in South Korea by utilizing a corpus-based approach. The term corpus (pl. corpora) is used to refer to electronic language data, that is, any collection of recorded instances of spoken or written language. A “MeToo” corpus has been collected by extracting newspaper articles containing the keyword “MeToo” from BIGKinds, big data analysis, and service and Nexis Uni, an online academic database search engine, to conduct this language analysis. The corpus analysis explores how Korean media represent accusers and the accused, victims and perpetrators. The extracted data includes 5,885 articles from four broadsheet newspapers (Chosun, JoongAng, Hangyore, and Kyunghyang) and 88 articles from two Korea-based English newspapers (Korea Times and Korea Herald) between January 2017 and November 2020. The information includes basic data analysis with respect to keyword frequency and network analysis and adds refined examinations of select corpus samples through naming strategies, semantic relations, and pragmatic properties. Along with the exponential increase of the number of articles containing the keyword “MeToo” from 104 articles in 2017 to 3,546 articles in 2018, the network and keyword analysis highlights ‘US,’ ‘Harvey Weinstein’, and ‘Hollywood,’ as keywords for 2017, with articles in 2018 highlighting ‘Seo Ji-Hyun, ‘politics,’ ‘President Moon,’ ‘An Ui-Jeong, ‘Lee Yoon-taek’ (the names of perpetrators), and ‘(Korean) society.’ This outcome demonstrates the shift of media focus from international affairs to domestic cases. Another crucial finding is that word ‘defamation’ is widely distributed in the “MeToo” corpus. This relates to the South Korean legal system, in which a person who defames another by publicly alleging information detrimental to their reputation—factual or fabricated—is punishable by law (Article 307 of the Criminal Act of Korea). If the defamation occurs on the internet, it is subject to aggravated punishment under the Act on Promotion of Information and Communications Network Utilization and Information Protection. These laws, in particular, have been used against accusers who have publicly come forward in the wake of “MeToo” in South Korea, adding an extra dimension of risk. This corpus analysis of “MeToo” newspaper articles contributes to the analysis of the media representation of the “MeToo” movement and sheds light on the shifting landscape of gender relations in the public sphere in South Korea.

Keywords: corpus linguistics, MeToo, newspapers, South Korea

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Authors: Loha Hashimy, Isabella Castillo

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In today's rapidly evolving technological landscape, the importance of precise navigation and mapping systems cannot be understated. As various sectors undergo transformative changes, the market potential for Advanced Mapping and Management Systems (AMMS) emerges as a critical focus area. The Galileo/GNSS-Based Autonomous Mobile Mapping System (GAMMS) project, specifically targeted toward high-definition mapping (HDM), endeavours to provide insights into this market within the broader context of the geomatics and navigation fields. With the growing integration of Autonomous Vehicles (AVs) into our transportation systems, the relevance and demand for sophisticated mapping solutions like HDM have become increasingly pertinent. The research employed a meticulous, lean, stepwise, and interconnected methodology to ensure a comprehensive assessment. Beginning with the identification of pivotal project results, the study progressed into a systematic market screening. This was complemented by an exhaustive desk research phase that delved into existing literature, data, and trends. To ensure the holistic validity of the findings, extensive consultations were conducted. Academia and industry experts provided invaluable insights through interviews, questionnaires, and surveys. This multi-faceted approach facilitated a layered analysis, juxtaposing secondary data with primary inputs, ensuring that the conclusions were both accurate and actionable. Our investigation unearthed a plethora of drivers steering the HD maps landscape. These ranged from technological leaps, nuanced market demands, and influential economic factors to overarching socio-political shifts. The meteoric rise of Autonomous Vehicles (AVs) and the shift towards app-based transportation solutions, such as Uber, stood out as significant market pull factors. A nuanced PESTEL analysis further enriched our understanding, shedding light on political, economic, social, technological, environmental, and legal facets influencing the HD maps market trajectory. Simultaneously, potential roadblocks were identified. Notable among these were barriers related to high initial costs, concerns around data quality, and the challenges posed by a fragmented and evolving regulatory landscape. The GAMMS project serves as a beacon, illuminating the vast opportunities that lie ahead for the HD mapping sector. It underscores the indispensable role of HDM in enhancing navigation, ensuring safety, and providing pinpoint, accurate location services. As our world becomes more interconnected and reliant on technology, HD maps emerge as a linchpin, bridging gaps and enabling seamless experiences. The research findings accentuate the imperative for stakeholders across industries to recognize and harness the potential of HD mapping, especially as we stand on the cusp of a transportation revolution heralded by Autonomous Vehicles and advanced geomatic solutions.

Keywords: high-definition mapping (HDM), autonomous vehicles, PESTEL analysis, market drivers

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Authors: Masoume Ehsani, Ning Zhu, Huu Doan, Ali Lohi, Amira Abdelrasoul

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Membrane fouling poses severe challenges in membrane-based wastewater treatment applications. Ultrasound (US) has been considered an effective fouling remediation technique in filtration processes. Bubble cavitation in the liquid medium results from the alternating rarefaction and compression cycles during the US irradiation at sufficiently high acoustic pressure. Cavitation microbubbles generated under US irradiation can cause eddy current and turbulent flow within the medium by either oscillating or discharging energy to the system through microbubble explosion. Turbulent flow regime and shear forces created close to the membrane surface cause disturbing the cake layer and dislodging the foulants, which in turn improve the cleaning efficiency and filtration performance. Therefore, the number, size, velocity, and oscillation pattern of the microbubbles created in the liquid medium play a crucial role in foulant detachment and permeate flux recovery. The goal of the current study is to gain in depth understanding of the influence of the US power intensity and frequency on the microbubble dynamics and its characteristics generated under US irradiation. In comparison with other imaging techniques, the synchrotron in-line Phase Contrast Imaging technique at the Canadian Light Source (CLS) allows in-situ observation and real-time visualization of microbubble dynamics. At CLS biomedical imaging and therapy (BMIT) polychromatic beamline, the effective parameters were optimized to enhance the contrast gas/liquid interface for the accuracy of the qualitative and quantitative analysis of bubble cavitation within the system. With the high flux of photons and the high-speed camera, a typical high projection speed was achieved; and each projection of microbubbles in water was captured in 0.5 ms. ImageJ software was used for post-processing the raw images for the detailed quantitative analyses of microbubbles. The imaging has been performed under the US power intensity levels of 50 W, 60 W, and 100 W, in addition to the US frequency levels of 20 kHz, 28 kHz, and 40 kHz. For the duration of 2 seconds of imaging, the effect of the US power and frequency on the average number, size, and fraction of the area occupied by bubbles were analyzed. Microbubbles’ dynamics in terms of their velocity in water was also investigated. For the US power increase of 50 W to 100 W, the average bubble number and the average bubble diameter were increased from 746 to 880 and from 36.7 µm to 48.4 µm, respectively. In terms of the influence of US frequency, a fewer number of bubbles were created at 20 kHz (average of 176 bubbles rather than 808 bubbles at 40 kHz), while the average bubble size was significantly larger than that of 40 kHz (almost seven times). The majority of bubbles were captured close to the membrane surface in the filtration unit. According to the study observations, membrane cleaning efficiency is expected to be improved at higher US power and lower US frequency due to the higher energy release to the system by increasing the number of bubbles or growing their size during oscillation (optimum condition is expected to be at 20 kHz and 100 W).

Keywords: bubble dynamics, cavitational bubbles, membrane fouling, ultrasonic cleaning

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Authors: Michael Picard

Abstract:

This proposal offers to shed light on the changing legal geography of the global waste economy. Global waste recycling has become a multi-billion-dollar industry. NASDAQ predicts the emergence of a worldwide 1,296G$ waste management market between 2017 and 2022. Underlining this evolution, a new generation of preferential waste-trade agreements has emerged in the Pacific. In the last decade, Japan has concluded a series of bilateral treaties with Asian countries, and most recently with China. An agreement between Tokyo and Beijing was formalized on 7 May 2008, which forged an economic partnership on waste transfer and mining. The agreement set up International Recycling Zones, where certified recycling plants in China process industrial waste imported from Japan. Under the joint venture, Chinese companies salvage the embedded value from Japanese industrial discards, reprocess them and send them back to Japanese manufacturers, such as Mitsubishi and Panasonic. This circular economy is designed to convert surplus garbage into surplus value. Ever since the opening of Sino-Japanese eco-parks, millions of tons of plastic and e-waste have been exported from Japan to China every year. Yet, quite unexpectedly, China has recently closed its waste market to imports, jeopardizing Japan’s billion-dollar exports to China. China notified the WTO that, by the end of 2017, it would no longer accept imports of plastics and certain metals. Given China’s share of Japanese waste exports, a complete closure of China’s market would require Japan to find new uses for its recyclable industrial trash generated domestically every year. It remains to be seen how China will effectively implement its ban on waste imports, considering the economic interests at stake. At this stage, what remains to be clarified is whether China's ban on waste imports will negatively affect the recycling trade between Japan and China. What is clear, though, is the rapid transformation in the legal geography of waste mining in East-Asia. For decades, East-Asian waste trade had been tied up in an ‘ecologically unequal exchange’ between the Japanese core and the Chinese periphery. This global unequal waste distribution could be measured by the Environmental Stringency Index, which revealed that waste regulation was 39% weaker in the Global South than in Japan. This explains why Japan could legally export its hazardous plastic and electronic discards to China. The asymmetric flow of hazardous waste between Japan and China carried the colonial heritage of international law. The legal geography of waste distribution was closely associated to the imperial construction of an ecological trade imbalance between the Japanese source and the Chinese sink. Thus, China’s recent decision to ban hazardous waste imports is a sign of a broader ecological shift. As a global economic superpower, China announced to the world it would no longer be the planet’s junkyard. The policy change will have profound consequences on the global circulation of waste, re-routing global waste towards countries south of China, such as Vietnam and Malaysia. By the time the Berlin Conference takes place in May 2018, the presentation will be able to assess more accurately the effect of the Chinese ban on the transboundary movement of waste in Asia.

Keywords: Asia, ecological unequal exchange, global waste trade, legal geography

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Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

Abstract:

Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

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Authors: Faheema Khan

Abstract:

To investigate the ability of sensitive and tolerant genotype of Glycine max to adapt to a saline environment in a field, we examined the growth performance, water relation and activities of antioxidant enzymes in relation to photosynthetic rate, chlorophyll a fluorescence, photosynthetic pigment concentration, protein and proline in plants exposed to salt stress. Ten soybean genotypes (Pusa-20, Pusa-40, Pusa-37, Pusa-16, Pusa-24, Pusa-22, BRAGG, PK-416, PK-1042, and DS-9712) were selected and grown hydroponically. After 3 days of proper germination, the seedlings were transferred to Hoagland’s solution (Hoagland and Arnon 1950). The growth chamber was maintained at a photosynthetic photon flux density of 430 μmol m−2 s−1, 14 h of light, 10 h of dark and a relative humidity of 60%. The nutrient solution was bubbled with sterile air and changed on alternate days. Ten-day-old seedlings were given seven levels of salt in the form of NaCl viz., T1 = 0 mM NaCl, T2=25 mM NaCl, T3=50 mM NaCl, T4=75 mM NaCl, T5=100 mM NaCl, T6=125 mM NaCl, T7=150 mM NaCl. The investigation showed that genotype Pusa-24, PK-416 and Pusa-20 appeared to be the most salt-sensitive. genotypes as inferred from their significantly reduced length, fresh weight and dry weight in response to the NaCl exposure. Pusa-37 appeared to be the most tolerant genotype since no significant effect of NaCl treatment on growth was found. We observed a greater decline in the photosynthetic variables like photosynthetic rate, chlorophyll fluorescence and chlorophyll content, in salt-sensitive (Pusa-24) genotype than in salt-tolerant Pusa-37 under high salinity. Numerous primers were verified on ten soybean genotypes obtained from Operon technologies among which 30 RAPD primers shown high polymorphism and genetic variation. The Jaccard’s similarity coefficient values for each pairwise comparison between cultivars were calculated and similarity coefficient matrix was constructed. The closer varieties in the cluster behaved similar in their response to salinity tolerance. Intra-clustering within the two clusters precisely grouped the 10 genotypes in sub-cluster as expected from their physiological findings.Salt tolerant genotype Pusa-37, was further analysed by 2-Dimensional gel electrophoresis to analyse the differential expression of proteins at high salt stress. In the Present study, 173 protein spots were identified. Of these, 40 proteins responsive to salinity were either up- or down-regulated in Pusa-37. Proteomic analysis in salt-tolerant genotype (Pusa-37) led to the detection of proteins involved in a variety of biological processes, such as protein synthesis (12 %), redox regulation (19 %), primary and secondary metabolism (25 %), or disease- and defence-related processes (32 %). In conclusion, the soybean plants in our study responded to salt stress by changing their protein expression pattern. The photosynthetic, biochemical and molecular study showed that there is variability in salt tolerance behaviour in soybean genotypes. Pusa-24 is the salt-sensitive and Pusa-37 is the salt-tolerant genotype. Moreover this study gives new insights into the salt-stress response in soybean and demonstrates the power of genomic and proteomic approach in plant biology studies which finally could help us in identifying the possible regulatory switches (gene/s) controlling the salt tolerant genotype of the crop plants and their possible role in defence mechanism.

Keywords: glycine max, salt stress, RAPD, genomic and proteomic variability

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

Abstract:

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

Abstract:

A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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Authors: Miroslav Premrov, Andrej Štrukelj, Erika Kozem Šilih

Abstract:

The utilization of prefabricated timber-wall elements with double glazing, called as double-skin façade element (DSF), represents an innovative structural approach in the context of new high-rise timber construction, simultaneously combining sustainable solutions with improved energy efficiency and living quality. In addition to the minimum energy needs of buildings, the design of modern buildings is also increasingly focused on the optimal indoor comfort, in particular on sufficient natural light indoors. An optimally energy-designed building with an optimal layout of glazed areas around the building envelope represents a great potential in modern timber construction. Usually, all these transparent façade elements, because of energy benefits, are primary asymmetrical oriented and if they are considered as non-resisting against a horizontal load impact, a strong torsion effects in the building can appear. The problem of structural stability against a strong horizontal load impact of such modern timber buildings especially increase in a case of high-rise structures where additional bracing elements have to be used. In such a case, special diagonal bracing systems or other bracing solutions with common timber wall elements have to be incorporated into the structure of the building to satisfy all prescribed resisting requirements given by the standards. However, all such structural solutions are usually not environmentally friendly and also not contribute to an improved living comfort, or they are not accepted by the architects at all. Consequently, it is a special need to develop innovative load-bearing timber-glass wall elements which are in the same time environmentally friendly, can increase internal comfort in the building, but are also load-bearing. The new developed load-bearing DSF elements can be a good answer on all these requirements. Timber-glass façade elements DSF wall elements consist of two transparent layers, thermal-insulated three-layered glass pane on the internal side and an additional single-layered glass pane on the external side of the wall. The both panes are separated by an air channel which can be of any dimensions and can have a significant influence on the thermal insulation or acoustic response of such a wall element. Most already published studies on DSF elements primarily deal only with energy and LCA solutions and do not address any structural problems. In previous studies according to experimental analysis and mathematical modeling it was already presented a possible benefit of such load-bearing DSF elements, especially comparing with previously developed load-bearing single-skin timber wall elements, but they were not applicate yet in any high-rise timber structure. Therefore, in the presented study specially selected 10-storey prefabricated timber building constructed in a cross-laminated timber (CLT) structural wall system is analyzed using the developed DSF elements in a sense to increase a structural lateral stability of the whole building. The results evidently highlight the importance the load-bearing DSF elements, as their incorporation can have a significant impact on the overall behavior of the structure through their influence on the stiffness properties. Taking these considerations into account is crucial to ensure compliance with seismic design codes and to improve the structural resilience of high-rise timber buildings.

Keywords: glass, high-rise buildings, numerical analysis, timber

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