Search results for: strong discontinuity
Commenced in January 2007
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Paper Count: 3283

Search results for: strong discontinuity

73 Determination of the Presence of Antibiotic Resistance from Vibrio Species in Northern Italy

Authors: Tramuta Clara, Masotti Chiara, Pitti Monica, Adriano Daniela, Battistini Roberta, Serraca Laura, Decastelli Lucia

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Oysters are considered filter organisms, and their raw consumption may increase health risks for consumers: it is often associated with outbreaks of gastroenteritis or enteric illnesses. Most of these foodborne diseases are caused by Vibrio strains, enteric pathogens also involved in the diffusion of genetic determinants of antibiotic resistance and their entrance along the food chain. The European Food Safety Authority (EFSA), during the European Union report on antimicrobial resistance in 2017, focused the attention about the role of food as a possible carrier of antibiotic-resistant bacteria or antibiotic-resistance genes that determine health risks for humans. This study wants to determine antibiotic resistance and antibiotic-resistance genes in Vibrio spp. isolated from Crassostrea gigas oysters collected in the Golfo della Spezia (Liguria, Italy). A total of 47 Vibrio spp. strains were isolated (ISO21872-2:2017) during the summer of 2021 from oysters of Crassostrea gigas. The strains were identified by MALDI-TOF (Bruker, Germany) mass spectrometry and tested for antibiotic susceptibility using a broth microdiluition method (ISO20776-1:2019) using Sensititre EUVSEC plates (Thermo-Fisher Scientific) to obtain the Minimum Inhibitory Concentration (MIC). The strains were tested with PCR-based biomolecular methods, according to previous works, to define the presence of 23 resistance genes of the main classes of antibiotics used in human and veterinary medicine: tet (B), tet (C), tet (D), tet (A), tet (E), tet (G ), tet (K), tet (L), tet (M), tet (O), tet (S) (tetracycline resistance); blaCTX-M, blaTEM, blaOXA, blaSHV (β-lactam resistance); mcr-1 and mcr-2 (colistin resistance); qnrA, qnrB, and qnrS (quinolone resistance); sul1, sul2 and sul3 (sulfonamide resistance). Six different species have been identified: V. alginolyticus 34% (n=16), V. harveyi 28% (n=13), V. fortis 15% (n=7), V. pelagius 8% (n=4), V. parahaemolyticus 11% (n=5) e V. chagasii 4% (n=2). The PCR assays showed the presence of the blaTEM gene on 40% of the strains (n=19). All the other genes were not detected, except for a V. alginolyticus positive for anrS gene. The broth microdiluition method results showed an high level of resistance for ciprofloxacin (62%; n=29), ampicillin (47%; n=22), and colistin (49%; n=23). Furthermore, 32% (n=15) of strains can be considered multiresistant bacteria for the simultaneous presence of resistance for three different antibiotic classes. Susceptibility towards meropenem, azithromycin, gentamicin, ceftazidime, cefotaxime, chloramphenicol, tetracycline and sulphamethoxazole reached 100%. The Vibrio species identified in this study are widespread in marine environments and can cause gastrointerstinal infections after the ingestion of raw fish products and bivalve molluscs. The level of resistance to antibiotics such as ampicillin, ciprofloxacin and colistin can be connected to anthropic factors (industrial, agricultural and domestic wastes) that promote the spread of resistance to these antibiotics. It can be also observed a strong correlation between phenotypic (resistant MIC) and genotypic (positive blaTEM gene) resistance for ampicillin on the same strains, probably due to the transfer of genetic material between bacterial strains. Consumption of raw bivalve molluscs can represent a risk for consumers heath due to the potentially presence of foodborne pathogens, highly resistant to different antibiotics and source of transferable antibiotic-resistant genes.

Keywords: vibrio species, blaTEM genes, antimicrobial resistance, PCR

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72 Delicate Balance between Cardiac Stress and Protection: Role of Mitochondrial Proteins

Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

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71 Effectiveness of an Intervention to Increase Physics Students' STEM Self-Efficacy: Results of a Quasi-Experimental Study

Authors: Stephanie J. Sedberry, William J. Gerace, Ian D. Beatty, Michael J. Kane

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Increasing the number of US university students who attain degrees in STEM and enter the STEM workforce is a national priority. Demographic groups vary in their rates of participation in STEM, and the US produces just 10% of the world’s science and engineering degrees (2014 figures). To address these gaps, we have developed and tested a practical, 30-minute, single-session classroom-based intervention to improve students’ self-efficacy and academic performance in University STEM courses. Self-efficacy is a psychosocial construct that strongly correlates with academic success. Self-efficacy is a construct that is internal and relates to the social, emotional, and psychological aspects of student motivation and performance. A compelling body of research demonstrates that university students’ self-efficacy beliefs are strongly related to their selection of STEM as a major, aspirations for STEM-related careers, and persistence in science. The development of an intervention to increase students’ self-efficacy is motivated by research showing that short, social-psychological interventions in education can lead to large gains in student achievement. Our intervention addresses STEM self-efficacy via two strong, but previously separate, lines of research into attitudinal/affect variables that influence student success. The first is ‘attributional retraining,’ in which students learn to attribute their successes and failures to internal rather than external factors. The second is ‘mindset’ about fixed vs. growable intelligence, in which students learn that the brain remains plastic throughout life and that they can, with conscious effort and attention to thinking skills and strategies, become smarter. Extant interventions for both of these constructs have significantly increased academic performance in the classroom. We developed a 34-item questionnaire (Likert scale) to measure STEM Self-efficacy, Perceived Academic Control, and Growth Mindset in a University STEM context, and validated it with exploratory factor analysis, Rasch analysis, and multi-trait multi-method comparison to coded interviews. Four iterations of our 42-week research protocol were conducted across two academic years (2017-2018) at three different Universities in North Carolina, USA (UNC-G, NC A&T SU, and NCSU) with varied student demographics. We utilized a quasi-experimental prospective multiple-group time series research design with both experimental and control groups, and we are employing linear modeling to estimate the impact of the intervention on Self-Efficacy,wth-Mindset, Perceived Academic Control, and final course grades (performance measure). Preliminary results indicate statistically significant effects of treatment vs. control on Self-Efficacy, Growth-Mindset, Perceived Academic Control. Analyses are ongoing and final results pending. This intervention may have the potential to increase student success in the STEM classroom—and ownership of that success—to continue in a STEM career. Additionally, we have learned a great deal about the complex components and dynamics of self-efficacy, their link to performance, and the ways they can be impacted to improve students’ academic performance.

Keywords: academic performance, affect variables, growth mindset, intervention, perceived academic control, psycho-social variables, self-efficacy, STEM, university classrooms

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70 Children’s Experience of the Built Environment in the Initial Stages of a Settlement Formation: Case Study of Shahid-Keshvari New Settlement, Isfahan, Iran

Authors: Hassan Sheikh, Mehdi Nilipour, Amiraslan Fila

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Many conventional town planning processes do little to give children and young people a voice on what is important about the urban environment. As a result of paying little attention to the children, their physical, social and mental needs are hardly met in urban environments. Therefore, urban spaces are impotent to attract children, while their recreational space has been confined to home or virtual spaces. Since children are just taking the first steps to learn the world beyond house borders, their living environment will profoundly influence almost all aspects of their lives. This puts a great deal of responsibility on the shoulders of planners, who need to balance a number of different issues in urban design to make places more child-friendly. The main purpose of present research is to analyze and plan a child-friendly environment in an on-going urban settlement development for the benefit of all residents. Assessing children’s needs and regard them in development strategies and policies will help to “plan for children”. Following this purpose, based on child-friendly environment studies, indicators of child-friendly environments were collected. Then three distinct characteristics of case study, which are being under-construction, lack of social ties between dwellers and high-rise building, determined seven indicators included basic services, Urban and environmental qualities, Family, kin, peers and community, Sense of belonging and continuity, participation, Safety, security and freedom of movement and human scale. With the survey, Informal observation and participation in small communities, essential data has been collected and analyzed by SPSS software. The field study is Shahid-Keshvari town in Isfahan, Iran. Eighty-six middle childhood, children (ages 8-13) participated. The results show Children's satisfaction is correlated with basic services and the quality of the environment, social environment and the safety and security. The considerable number of children and youth (55%) like to live somewhere other than the town. Satisfaction and sense of belonging and continuity have a strong inverse correlation with age. In other words, as age increases, satisfaction and consequently a sense of belonging will be reduced; thus children and youth consider their future somewhere out of the town. The main reason for dissatisfaction was the basic services and social environment. More than half of children (55%) expressed their wish to develop basic services in terms of availability, hierarchy, and quality. Among all recreational places, children showed more interest to the parks. About three-quarters (76%) considered building a park as a crucial item for residents. The significant number of children (54%) want to have a relationship with more friends. This could be due to the serious shortage of the leisure spaces such as parks or playgrounds. Also, the space around the house or space between the apartments has not been designed for play or children’s activities. Moreover, the presence of strangers and construction workers have a negative impact on children's sense of peace and security; 60% of children are afraid of theft and 36% of children found strangers as a menace. The analysis of children’s issues and suggestions provides an insight to plan and design of child-friendly environment in new towns.

Keywords: child-friendly city (CFC), child-friendly environment, child participation, under-construction environment, Isfahan Shahid-Keshvari Town

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69 Medicompills Architecture: A Mathematical Precise Tool to Reduce the Risk of Diagnosis Errors on Precise Medicine

Authors: Adriana Haulica

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Powered by Machine Learning, Precise medicine is tailored by now to use genetic and molecular profiling, with the aim of optimizing the therapeutic benefits for cohorts of patients. As the majority of Machine Language algorithms come from heuristics, the outputs have contextual validity. This is not very restrictive in the sense that medicine itself is not an exact science. Meanwhile, the progress made in Molecular Biology, Bioinformatics, Computational Biology, and Precise Medicine, correlated with the huge amount of human biology data and the increase in computational power, opens new healthcare challenges. A more accurate diagnosis is needed along with real-time treatments by processing as much as possible from the available information. The purpose of this paper is to present a deeper vision for the future of Artificial Intelligence in Precise medicine. In fact, actual Machine Learning algorithms use standard mathematical knowledge, mostly Euclidian metrics and standard computation rules. The loss of information arising from the classical methods prevents obtaining 100% evidence on the diagnosis process. To overcome these problems, we introduce MEDICOMPILLS, a new architectural concept tool of information processing in Precise medicine that delivers diagnosis and therapy advice. This tool processes poly-field digital resources: global knowledge related to biomedicine in a direct or indirect manner but also technical databases, Natural Language Processing algorithms, and strong class optimization functions. As the name suggests, the heart of this tool is a compiler. The approach is completely new, tailored for omics and clinical data. Firstly, the intrinsic biological intuition is different from the well-known “a needle in a haystack” approach usually used when Machine Learning algorithms have to process differential genomic or molecular data to find biomarkers. Also, even if the input is seized from various types of data, the working engine inside the MEDICOMPILLS does not search for patterns as an integrative tool. This approach deciphers the biological meaning of input data up to the metabolic and physiologic mechanisms, based on a compiler with grammars issued from bio-algebra-inspired mathematics. It translates input data into bio-semantic units with the help of contextual information iteratively until Bio-Logical operations can be performed on the base of the “common denominator “rule. The rigorousness of MEDICOMPILLS comes from the structure of the contextual information on functions, built to be analogous to mathematical “proofs”. The major impact of this architecture is expressed by the high accuracy of the diagnosis. Detected as a multiple conditions diagnostic, constituted by some main diseases along with unhealthy biological states, this format is highly suitable for therapy proposal and disease prevention. The use of MEDICOMPILLS architecture is highly beneficial for the healthcare industry. The expectation is to generate a strategic trend in Precise medicine, making medicine more like an exact science and reducing the considerable risk of errors in diagnostics and therapies. The tool can be used by pharmaceutical laboratories for the discovery of new cures. It will also contribute to better design of clinical trials and speed them up.

Keywords: bio-semantic units, multiple conditions diagnosis, NLP, omics

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68 Emotional State and Cognitive Workload during a Flight Simulation: Heart Rate Study

Authors: Damien Mouratille, Antonio R. Hidalgo-Muñoz, Nadine Matton, Yves Rouillard, Mickael Causse, Radouane El Yagoubi

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Background: The monitoring of the physiological activity related to mental workload (MW) on pilots will be useful to improve aviation safety by anticipating human performance degradation. The electrocardiogram (ECG) can reveal MW fluctuations due to either cognitive workload or/and emotional state since this measure exhibits autonomic nervous system modulations. Arguably, heart rate (HR) is one of its most intuitive and reliable parameters. It would be particularly interesting to analyze the interaction between cognitive requirements and emotion in ecologic sets such as a flight simulator. This study aims to explore by means of HR the relation between cognitive demands and emotional activation. Presumably, the effects of cognition and emotion overloads are not necessarily cumulative. Methodology: Eight healthy volunteers in possession of the Private Pilot License were recruited (male; 20.8±3.2 years). ECG signal was recorded along the whole experiment by placing two electrodes on the clavicle and left pectoral of the participants. The HR was computed within 4 minutes segments. NASA-TLX and Big Five inventories were used to assess subjective workload and to consider the influence of individual personality differences. The experiment consisted in completing two dual-tasks of approximately 30 minutes of duration into a flight simulator AL50. Each dual-task required the simultaneous accomplishment of both a pre-established flight plan and an additional task based on target stimulus discrimination inserted between Air Traffic Control instructions. This secondary task allowed us to vary the cognitive workload from low (LC) to high (HC) levels, by combining auditory and visual numerical stimuli to respond to meeting specific criteria. Regarding emotional condition, the two dual-tasks were designed to assure analogous difficulty in terms of solicited cognitive demands. The former was realized by the pilot alone, i.e. Low Arousal (LA) condition. In contrast, the latter generates a high arousal (HA), since the pilot was supervised by two evaluators, filmed and involved into a mock competition with the rest of the participants. Results: Performance for the secondary task showed significant faster reaction times (RT) for HA compared to LA condition (p=.003). Moreover, faster RT was found for LC compared to HC (p < .001) condition. No interaction was found. Concerning HR measure, despite the lack of main effects an interaction between emotion and cognition is evidenced (p=.028). Post hoc analysis showed smaller HR for HA compared to LA condition only for LC (p=.049). Conclusion. The control of an aircraft is a very complex task including strong cognitive demands and depends on the emotional state of pilots. According to the behavioral data, the experimental set has permitted to generate satisfactorily different emotional and cognitive levels. As suggested by the interaction found in HR measure, these two factors do not seem to have a cumulative impact on the sympathetic nervous system. Apparently, low cognitive workload makes pilots more sensitive to emotional variations. These results hint the independency between data processing and emotional regulation. Further physiological data are necessary to confirm and disentangle this relation. This procedure may be useful for monitoring objectively pilot’s mental workload.

Keywords: cognitive demands, emotion, flight simulator, heart rate, mental workload

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67 Use of Artificial Intelligence and Two Object-Oriented Approaches (k-NN and SVM) for the Detection and Characterization of Wetlands in the Centre-Val de Loire Region, France

Authors: Bensaid A., Mostephaoui T., Nedjai R.

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Nowadays, wetlands are the subject of contradictory debates opposing scientific, political and administrative meanings. Indeed, given their multiple services (drinking water, irrigation, hydrological regulation, mineral, plant and animal resources...), wetlands concentrate many socio-economic and biodiversity issues. In some regions, they can cover vast areas (>100 thousand ha) of the landscape, such as the Camargue area in the south of France, inside the Rhone delta. The high biological productivity of wetlands, the strong natural selection pressures and the diversity of aquatic environments have produced many species of plants and animals that are found nowhere else. These environments are tremendous carbon sinks and biodiversity reserves depending on their age, composition and surrounding environmental conditions, wetlands play an important role in global climate projections. Covering more than 3% of the earth's surface, wetlands have experienced since the beginning of the 1990s a tremendous revival of interest, which has resulted in the multiplication of inventories, scientific studies and management experiments. The geographical and physical characteristics of the wetlands of the central region conceal a large number of natural habitats that harbour a great biological diversity. These wetlands, one of the natural habitats, are still influenced by human activities, especially agriculture, which affects its layout and functioning. In this perspective, decision-makers need to delimit spatial objects (natural habitats) in a certain way to be able to take action. Thus, wetlands are no exception to this rule even if it seems to be a difficult exercise to delimit a type of environment as whose main characteristic is often to occupy the transition between aquatic and terrestrial environment. However, it is possible to map wetlands with databases, derived from the interpretation of photos and satellite images, such as the European database Corine Land cover, which allows quantifying and characterizing for each place the characteristic wetland types. Scientific studies have shown limitations when using high spatial resolution images (SPOT, Landsat, ASTER) for the identification and characterization of small wetlands (1 hectare). To address this limitation, it is important to note that these wetlands generally represent spatially complex features. Indeed, the use of very high spatial resolution images (>3m) is necessary to map small and large areas. However, with the recent evolution of artificial intelligence (AI) and deep learning methods for satellite image processing have shown a much better performance compared to traditional processing based only on pixel structures. Our research work is also based on spectral and textural analysis on THR images (Spot and IRC orthoimage) using two object-oriented approaches, the nearest neighbour approach (k-NN) and the Super Vector Machine approach (SVM). The k-NN approach gave good results for the delineation of wetlands (wet marshes and moors, ponds, artificial wetlands water body edges, ponds, mountain wetlands, river edges and brackish marshes) with a kappa index higher than 85%.

Keywords: land development, GIS, sand dunes, segmentation, remote sensing

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66 Foucault and Governmentality: International Organizations and State Power

Authors: Sara Dragisic

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Using the theoretical analysis of the birth of biopolitics that Foucault performed through the history of liberalism and neoliberalism, in this paper we will try to show how, precisely through problematizing the role of international institutions, the model of governance differs from previous ways of objectifying body and life. Are the state and its mechanisms still a Leviathan to fight against, or can it be even the driver of resistance against the proponents of modern governance and the biopolitical power? Do paradigmatic examples of biopolitics still appear through sovereignty and (international) law, or is it precisely this sphere that shows a significant dose of incompetence and powerlessness in relation to, not only the economic sphere (Foucault’s critique of neoliberalism) but also the new politics of freedom? Have the struggle for freedom and human rights, as well as the war on terrorism, opened a new spectrum of biopolitical processes, which are manifested precisely through new international institutions and humanitarian discourse? We will try to answer these questions, in the following way. On the one hand, we will show that the views of authors such as Agamben and Hardt and Negri, in whom the state and sovereignty are seen as enemies to be defeated or overcome, fail to see how such attempts could translate into the politicization of life like it is done in many examples through the doctrine of liberal interventionism and humanitarianism. On the other hand, we will point out that it is precisely the humanitarian discourse and the defense of the right to intervention that can be the incentive and basis for the politicization of the category of life and lead to the selective application of human rights. Zizek example of the killing of United Nations workers and doctors in a village during the Vietnam War, who were targeted even before police or soldiers, because they were precisely seen as a powerful instrument of American imperialism (as they were sincerely trying to help the population), will be focus of this part of the analysis. We’ll ask the question whether such interpretation is a kind of liquidation of the extreme left of the political (Laclau) or on this basis can be explained at least in part the need to review the functioning of international organizations, ranging from those dealing with humanitarian aid (and humanitarian military interventions) to those dealing with protection and the security of the population, primarily from growing terrorism. Based on the above examples, we will also explain how the discourse of terrorism itself plays a dual role: it can appear as a tool of liberal biopolitics, although, more superficially, it mostly appears as an enemy that wants to destroy the liberal system and its values. This brings us to the basic problem that this paper will tackle: do the mechanisms of institutional struggle for human rights and freedoms, which is often seen as opposed to the security mechanisms of the state, serve the governance of citizens in such a way that the latter themselves participate in producing biopolitical governmental practices? Is the freedom today "nothing but the correlative development of apparatuses of security" (Foucault)? Or, we can continue this line of Foucault’s argumentation and enhance the interpretation with the important question of what precisely today reflects the change in the rationality of governance in which society is transformed from a passive object into a subject of its own production. Finally, in order to understand the skills of biopolitical governance in modern civil society, it is necessary to pay attention to the status of international organizations, which seem to have become a significant place for the implementation of global governance. In this sense, the power of sovereignty can turn out to be an insufficiently strong power of security policy, which can go hand in hand with freedom policies, through neoliberal governmental techniques.

Keywords: neoliberalism, Foucault, sovereignty, biopolitics, international organizations, NGOs, Agamben, Hardt&Negri, Zizek, security, state power

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65 The Vanishing Treasure: An Anthropological Study on Changing Social Relationships, Values, Belief System and Language Pattern of the Limbus in Kalimpong Sub-Division of the Darjeeling District in West Bengal, India

Authors: Biva Samadder, Samita Manna

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India is a melting pot of races, tribes, castes and communities. The population of India can be roughly branched into the huge majority of “Civilized” Indians of the Plains and the minority of Tribal population of the hill area and the forest who constituting almost 16 percent of total population of India. The Kirat community composed of four ethnic tribes: Limbu, Lepcha, Dhimal, and Rai. These Kirat people were found to be rich in indigenous knowledge, skill and practices especially for the use on medicinal plants and livelihood purposes. The “Mundhum" is the oral scripture or the “Bible of the Limbus” which serves as the canon of the codes of the Limbu socialization, their moral values and the very orientation of their lifestyle. From birth till death the Limbus are disciplined in the life with full of religious rituals, traditions and culture governed by community norms with a rich legacy of indigenous knowledge and traditional practices. The present study has been conducted using both secondary as well as primary data by applying social methodology consisting of the social survey, questionnaire, interviews and observations in the Kalimpong Block-I of Darjeeling District of west Bengal of India, which is a heterogeneous zone in terms of its ethnic composition and where the Limbus are pre-dominantly concentrated. Due to their close contact with other caste and communities Limbus are now adjusted with the changing situation by borrowing some cultural traits from the other communities and changes that have taken place in their cultural practices, religious beliefs, economic aspects, languages and in social roles and relationships which is bringing the change in their material culture. Limbu language is placed in the Tibeto- Burman Language category. But due to the political and cultural domination of educationally sound and numerically dominant Bengali race, the different communities in this area forced to come under the one umbrella of the Nepali or Gorkhali nation (nation-people). Their respective identities had to be submerged in order to constitute as a strong force to resist Nepali domination and ensure their common survival. As Nepali is a lingua-franca of the area knowing and speaking Nepali language helps them in procuring economic and occupational facilities. Ironically, present day younger generation does not feel comfortable speaking in their own Limbu tongue. The traditional knowledge about medicinal plants, healing, and health culture is found to be wear away due to the lack of interest of young generation. Not only poverty, along with exclusion due to policies they are in the phase of extinction, but their capabilities are ignored and not documented and preserved especially in the case of Limbus who having a great cultural heritage of an oral tradition. Attempts have been made to discuss the persistence and changes in socioeconomic pattern of life in relation to the social structure, material culture, cultural practices, social relationships, indigenous technology, ethos and their values and belief system.

Keywords: changing social relationship, cultural transition, identity, indigenous knowledge, language

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64 Addressing the Gap in Health and Wellbeing Evidence for Urban Real Estate Brownfield Asset Management Social Needs and Impact Analysis Using Systems Mapping Approach

Authors: Kathy Pain, Nalumino Akakandelwa

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The study explores the potential to fill a gap in health and wellbeing evidence for purposeful urban real estate asset management to make investment a powerful force for societal good. Part of a five-year programme investigating the root causes of unhealthy urban development funded by the United Kingdom Prevention Research Partnership (UKPRP), the study pilots the use of a systems mapping approach to identify drivers and barriers to the incorporation of health and wellbeing evidence in urban brownfield asset management decision-making. Urban real estate not only provides space for economic production but also contributes to the quality of life in the local community. Yet market approaches to urban land use have, until recently, insisted that neo-classical technology-driven efficient allocation of economic resources should inform acquisition, operational, and disposal decisions. Buildings in locations with declining economic performance have thus been abandoned, leading to urban decay. Property investors are recognising the inextricable connection between sustainable urban production and quality of life in local communities. The redevelopment and operation of brownfield assets recycle existing buildings, minimising embodied carbon emissions. It also retains established urban spaces with which local communities identify and regenerate places to create a sense of security, economic opportunity, social interaction, and quality of life. Social implications of urban real estate on health and wellbeing and increased adoption of benign sustainability guidance in urban production are driving the need to consider how they affect brownfield real estate asset management decisions. Interviews with real estate upstream decision-makers in the study, find that local social needs and impact analysis is becoming a commercial priority for large-scale urban real estate development projects. Evidence of the social value-added of proposed developments is increasingly considered essential to secure local community support and planning permissions, and to attract sustained inward long-term investment capital flows for urban projects. However, little is known about the contribution of population health and wellbeing to socially sustainable urban projects and the monetary value of the opportunity this presents to improve the urban environment for local communities. We report early findings from collaborations with two leading property companies managing major investments in brownfield urban assets in the UK to consider how the inclusion of health and wellbeing evidence in social valuation can inform perceptions of brownfield development social benefit for asset managers, local communities, public authorities and investors for the benefit of all parties. Using holistic case studies and systems mapping approaches, we explore complex relationships between public health considerations and asset management decisions in urban production. Findings indicate a strong real estate investment industry appetite and potential to include health as a vital component of sustainable real estate social value creation in asset management strategies.

Keywords: brownfield urban assets, health and wellbeing, social needs and impact, social valuation, sustainable real estate, systems mapping

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63 Complex Dynamics in a Morphologically Heterogeneous Biological Medium

Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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62 Seroprevalence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) Infection among Healthy and High Risk Individuals in Qatar

Authors: Raham El-Kahlout, Hadi Yassin, Asmaa Athani, Marwan Abou Madi, Gheyath Nasrallah

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Background: Since its first isolation in September 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has diffused across 27 countries infecting more than two thousand individuals with a high case fatality rate. MERS-CoV–specific antibodies are widely found in Dromedary camel along with viral shedding of similar viruses detected in human at same region, suggesting that MERS epidemiology may be central role by camel. Interestingly, MERS-CoV has also been also reported to be asymptomatic or to cause influenza-like mild illnesses. Therefore, in a country like Qatar (bordered Saudi Arabia), where camels are widely spread, serological surveys are important to explore the role of camels in MERS-CoV transmission. However, widespread strategic serological surveillances of MERS-CoV among populations, particularly in endemic country, are infrequent. In the absence of clear epidemiological view, cross-sectional MERS antibody surveillances in human populations are of global concern. Method: We performed a comparative serological screening of 4719 healthy blood donors, 135 baseline case contacts (high risk individual), and four MERS confirmed patients (by PCR) for the presence of anti-MERS IgG. Initially, samples were screened using Euroimmune anti- MERS-CoV IgG ELISA kit, the only commercial kit available in the market and recommended by the CDC as a screening kit. To confirm ELISA test results, farther serological testing was performed for all borderline and positive samples using two assays; the anti MERS-CoV IgG and IgM Euroimmune indirect immunofluorescent test (IIFT) and pseudoviral particle neutralizing assay (PPNA). Additionally, to test cross reactivity of anti-MERS-CoV antibody with other family members of coronavirus, borderline and positive samples were tested for the presence of the of IgG antibody of the following viruses; SARS, HCoV-229E, HKU1 using the Euroimmune IIFT for SARS and HCoV-229E and ELISA for HKU1. Results: In all of 4858 screened 15 samples [10 donors (0.21%, 10/4719), 1 case contact (0.77 %, 1/130), 3 patients (75%, 3/4)] anti-MERS IgG reactive/borderline samples were seen in ELISA. However, only 7 (0.14%) of them gave positive with in IIFT and only 3 (0.06%) was confirmed by the specific anti-MERS PPNA. One of the interesting findings was, a donor, who was selected in the control group as a negative anti-MERS IgG ELISA, yield reactive for anti-MERS IgM IIFT and was confirmed with the PPNA. Further, our preliminary results showed that there was a strong cross reactivity between anti- MERS-COV IgG with both HCoV-229E or anti-HKU1 IgG, yet, no cross reactivity of SARS were found. Conclusions: Our findings suggest that MERS-CoV is not heavily circulated among the population of Qatar and this is also indicated by low number of confirmed cases (only 18) since 2012. Additionally, the presence of antibody of other pathogenic human coronavirus may cause false positive results of both ELISA and IIFT, which stress the need for more evaluation studies for the available serological assays. Conclusion: this study provides an insight about the epidemiological view for MERS-CoV in Qatar population. It also provides a performance evaluation for the available serologic tests for MERS-CoV in a view of serologic status to other human coronaviruses.

Keywords: seroprevalence, MERS-CoV, healthy individuals, Qatar

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61 Unpacking the Spatial Outcomes of Public Transportation in a Developing Country Context: The Case of Johannesburg

Authors: Adedayo B. Adegbaju, Carel B. Schoeman, Ilse M. Schoeman

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The unique urban contexts that emanated from the apartheid history of South Africa informed the transport landscape of the City of Johannesburg. Apartheid‘s divisive spatial planning and land use management policies promoted sprawling and separated workers from job opportunities. This was further exacerbated by poor funding of public transport and road designs that encouraged the use of private cars. However, the democratization of the country in 1994 and the hosting of the 2010 FIFA World Cup provided a new impetus to the city’s public transport-oriented urban planning inputs. At the same time, the state’s new approach to policy formulations that entails the provision of public transport as one of the tools to end years of marginalization and inequalities soon began to largely reflect in planning decisions of other spheres of government. The Rea Vaya BRT and the Gautrain were respectively implemented by the municipal and provincial governments to demonstrate strong political will and commitment to the new policy direction. While the Gautrain was implemented to facilitate elite movement within Gauteng and to crowd investments and economic growths around station nodes, the BRT was provided for previously marginalized public transport users to provide a sustainable alternative to the dominant minibus taxi. The aim of this research is to evaluate the spatial impacts of the Gautrain and Rea Vaya BRT on the City of Johannesburg and to inform future outcomes by determining the existing potentials. By using the case study approach with a focus on the BRT and fast rail in a metropolitan context, the triangulation research method, which combines various data collection methods, was used to determine the research outcomes. The use of interviews, questionnaires, field observation, and databases such as REX, Quantec, StatsSA, GCRO observatory, national and provincial household travel surveys, and the quality of life surveys provided the basis for data collection. The research concludes that the Gautrain has demonstrated that viable alternatives to the private car can be provided, with its satisfactory feedbacks from users; while some of its station nodes (Sandton, Rosebank) have shown promises of transit-oriented development, one of the project‘s key objectives. The other stations have been unable to stimulate growth due to reasons like non-implementation of their urban design frameworks and lack of public sector investment required to attract private investors. The Rea Vaya BRT continues to be expanded in spite of both its inability to induce modal change and its low ridership figures. The research identifies factors like the low peak to base ratio, pricing, and the city‘s disjointed urban fabric as some of the reasons for its below-average performance. By drawing from the highlights and limitations, the study recommends that public transport provision should be institutionally integrated across and within spheres of government. Similarly, harmonization of the funding structure, better understanding of users’ needs, and travel patterns, underlined with continuity of policy direction and objectives, will equally promote optimal outcomes.

Keywords: bus rapid transit, Gautrain, Rea Vaya, sustainable transport, spatial and transport planning, transit oriented development

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60 Widely Diversified Macroeconomies in the Super-Long Run Casts a Doubt on Path-Independent Equilibrium Growth Model

Authors: Ichiro Takahashi

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One of the major assumptions of mainstream macroeconomics is the path independence of capital stock. This paper challenges this assumption by employing an agent-based approach. The simulation results showed the existence of multiple "quasi-steady state" equilibria of the capital stock, which may cast serious doubt on the validity of the assumption. The finding would give a better understanding of many phenomena that involve hysteresis, including the causes of poverty. The "market-clearing view" has been widely shared among major schools of macroeconomics. They understand that the capital stock, the labor force, and technology, determine the "full-employment" equilibrium growth path and demand/supply shocks can move the economy away from the path only temporarily: the dichotomy between the short-run business cycles and the long-run equilibrium path. The view then implicitly assumes the long-run capital stock to be independent of how the economy has evolved. In contrast, "Old Keynesians" have recognized fluctuations in output as arising largely from fluctuations in real aggregate demand. It will then be an interesting question to ask if an agent-based macroeconomic model, which is known to have path dependence, can generate multiple full-employment equilibrium trajectories of the capital stock in the super-long run. If the answer is yes, the equilibrium level of capital stock, an important supply-side factor, would no longer be independent of the business cycle phenomenon. This paper attempts to answer the above question by using the agent-based macroeconomic model developed by Takahashi and Okada (2010). The model would serve this purpose well because it has neither population growth nor technology progress. The objective of the paper is twofold: (1) to explore the causes of long-term business cycle, and (2) to examine the super-long behaviors of the capital stock of full-employment economies. (1) The simulated behaviors of the key macroeconomic variables such as output, employment, real wages showed widely diversified macro-economies. They were often remarkably stable but exhibited both short-term and long-term fluctuations. The long-term fluctuations occur through the following two adjustments: the quantity and relative cost adjustments of capital stock. The first one is obvious and assumed by many business cycle theorists. The reduced aggregate demand lowers prices, which raises real wages, thereby decreasing the relative cost of capital stock with respect to labor. (2) The long-term business cycles/fluctuations were synthesized with the hysteresis of real wages, interest rates, and investments. In particular, a sequence of the simulation runs with a super-long simulation period generated a wide range of perfectly stable paths, many of which achieved full employment: all the macroeconomic trajectories, including capital stock, output, and employment, were perfectly horizontal over 100,000 periods. Moreover, the full-employment level of capital stock was influenced by the history of unemployment, which was itself path-dependent. Thus, an experience of severe unemployment in the past kept the real wage low, which discouraged a relatively costly investment in capital stock. Meanwhile, a history of good performance sometimes brought about a low capital stock due to a high-interest rate that was consistent with a strong investment.

Keywords: agent-based macroeconomic model, business cycle, hysteresis, stability

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59 Transformation of Bangladesh Society: The Role of Religion

Authors: Abdul Wohab

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Context: The role of religion in the transformation of Bangladesh society has been significant since 1975. There has been a rise in religious presence, particularly Islam, in both private and public spheres supported by the state apparatuses. In 2009, a 'secular' political party came into power for the second time since independence and initiated the modernization of religious education systems. This research focuses on the transformation observed among the educated middle class who now prefer their children to attend modern, English medium madrasas that offer both religion-based and secular education. Research Aim: This research aims to investigate two main questions: a) what motivates the educated middle class to send their children to madrasa education? b) To what extent can it be argued that Bangladeshi society is transforming from its secular nature to being more religious?Methodology: The research applies a combination of primary and secondary methods. Case studies serve as the primary method, allowing for an in-depth exploration of the motivations of the educated middle class. The secondary method involves analyzing published news articles, op-eds, and websites related to madrasa education, as well as studying the reading syllabus of Aliya and Qwami madrasas in Bangladesh. Findings: Preliminary findings indicate that the educated middle class chooses madrasa education for reasons such as remembering and praying for their departed relatives, keeping their children away from substance abuse, fostering moral and ethical values, and instilling respect for seniors and relatives. The research also reveals that religious education is believed to help children remain morally correct according to the Quran and Hadith. Additionally, the establishment of madrasas in Bangladesh is attributed to economic factors, with demand and supply mechanisms playing a significant role. Furthermore, the findings suggest that government-run primary education institutions in rural areas face more challenges in enrollment compared to religious educational institutions like madrasas. Theoretical Importance: This research contributes to the understanding of societal transformation and the role of religion in this process. By examining the case of Bangladesh, it provides insights into how religion influences education choices and societal values. Data Collection and Analysis Procedures: Data for this research is collected through case studies, including interviews and observations of educated middle-class families who send their children to madrasas. In addition, analysis is conducted on relevant published materials such as news articles, op-eds, and websites. The reading syllabus of Aliya and Qwami madrasas is also analyzed to gain a comprehensive understanding of the education system. Questions Addressed: The research addresses two questions: a) what motivates the educated middle class to choose madrasa education for their children? b) To what extent can it be argued that Bangladeshi society is transforming from its secular nature to being more religious?Conclusion: The preliminary findings of this research highlight the motivations of the educated middle class in opting for madrasa education, including the desire to maintain religious traditions, promote moral values, and provide a strong foundation for their children. It also suggests that Bangladeshi society is experiencing a transformation towards a more religious orientation. This research contributes to the understanding of societal changes and the role of religion within Bangladesh, shedding light on the complex dynamics between religion and education.

Keywords: madrasa education, transformation, Bangladesh, religion and society, education

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58 Familial Exome Sequencing to Decipher the Complex Genetic Basis of Holoprosencephaly

Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

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Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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57 Describing Cognitive Decline in Alzheimer's Disease via a Picture Description Writing Task

Authors: Marielle Leijten, Catherine Meulemans, Sven De Maeyer, Luuk Van Waes

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For the diagnosis of Alzheimer's disease (AD), a large variety of neuropsychological tests are available. In some of these tests, linguistic processing - both oral and written - is an important factor. Language disturbances might serve as a strong indicator for an underlying neurodegenerative disorder like AD. However, the current diagnostic instruments for language assessment mainly focus on product measures, such as text length or number of errors, ignoring the importance of the process that leads to written or spoken language production. In this study, it is our aim to describe and test differences between cognitive and impaired elderly on the basis of a selection of writing process variables (inter- and intrapersonal characteristics). These process variables are mainly related to pause times, because the number, length, and location of pauses have proven to be an important indicator of the cognitive complexity of a process. Method: Participants that were enrolled in our research were chosen on the basis of a number of basic criteria necessary to collect reliable writing process data. Furthermore, we opted to match the thirteen cognitively impaired patients (8 MCI and 5 AD) with thirteen cognitively healthy elderly. At the start of the experiment, participants were each given a number of tests, such as the Mini-Mental State Examination test (MMSE), the Geriatric Depression Scale (GDS), the forward and backward digit span and the Edinburgh Handedness Inventory (EHI). Also, a questionnaire was used to collect socio-demographic information (age, gender, eduction) of the subjects as well as more details on their level of computer literacy. The tests and questionnaire were followed by two typing tasks and two picture description tasks. For the typing tasks participants had to copy (type) characters, words and sentences from a screen, whereas the picture description tasks each consisted of an image they had to describe in a few sentences. Both the typing and the picture description tasks were logged with Inputlog, a keystroke logging tool that allows us to log and time stamp keystroke activity to reconstruct and describe text production processes. The main rationale behind keystroke logging is that writing fluency and flow reveal traces of the underlying cognitive processes. This explains the analytical focus on pause (length, number, distribution, location, etc.) and revision (number, type, operation, embeddedness, location, etc.) characteristics. As in speech, pause times are seen as indexical of cognitive effort. Results. Preliminary analysis already showed some promising results concerning pause times before, within and after words. For all variables, mixed effects models were used that included participants as a random effect and MMSE scores, GDS scores and word categories (such as determiners and nouns) as a fixed effect. For pause times before and after words cognitively impaired patients paused longer than healthy elderly. These variables did not show an interaction effect between the group participants (cognitively impaired or healthy elderly) belonged to and word categories. However, pause times within words did show an interaction effect, which indicates pause times within certain word categories differ significantly between patients and healthy elderly.

Keywords: Alzheimer's disease, keystroke logging, matching, writing process

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56 Geochemical Evaluation of Metal Content and Fluorescent Characterization of Dissolved Organic Matter in Lake Sediments

Authors: Fani Sakellariadou, Danae Antivachis

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Purpose of this paper is to evaluate the environmental status of a coastal Mediterranean lake, named Koumoundourou, located in the northeastern coast of Elefsis Bay, in the western region of Attiki in Greece, 15 km far from Athens. It is preserved from ancient times having an important archaeological interest. Koumoundourou lake is also considered as a valuable wetland accommodating an abundant flora and fauna, with a variety of bird species including a few world’s threatened ones. Furthermore, it is a heavily modified lake, affected by various anthropogenic pollutant sources which provide industrial, urban and agricultural contaminants. The adjacent oil refineries and the military depot are the major pollution providers furnishing with crude oil spills and leaks. Moreover, the lake accepts a quantity of groundwater leachates from the major landfill of Athens. The environmental status of the lake results from the intensive land uses combined with the permeable lithology of the surrounding area and the existence of karstic springs which discharge calcareous mountains. Sediment samples were collected along the shoreline of the lake using a Van Veen grab stainless steel sampler. They were studied for the determination of the total metal content and the metal fractionation in geochemical phases as well as the characterization of the dissolved organic matter (DOM). These constituents have a significant role in the ecological consideration of the lake. Metals may be responsible for harmful environmental impacts. The metal partitioning offers comprehensive information for the origin, mode of occurrence, biological and physicochemical availability, mobilization and transport of metals. Moreover, DOM has a multifunctional importance interacting with inorganic and organic contaminants leading to biogeochemical and ecological effects. The samples were digested using microwave heating with a suitable laboratory microwave unit. For the total metal content, the samples were treated with a mixture of strong acids. Then, a sequential extraction procedure was applied for the removal of exchangeable, carbonate hosted, reducible, organic/sulphides and residual fractions. Metal content was determined by an ICP-MS (Perkin Elmer, ICP MASS Spectrophotometer NexION 350D). Furthermore, the DOM was removed via a gentle extraction procedure and then it was characterized by fluorescence spectroscopy using a Perkin-Elmer LS 55 luminescence spectrophotometer equipped with the WinLab 4.00.02 software for data processing (Agilent, Cary Eclipse Fluorescence). Mono dimensional emission, excitation, synchronous-scan excitation and total luminescence spectra were recorded for the classification of chromophoric units present in the aqueous extracts. Total metal concentrations were determined and compared with those of the Elefsis gulf sediments. Element partitioning showed the anthropogenic sources and the contaminant bioavailability. All fluorescence spectra, as well as humification indices, were evaluated in detail to find out the nature and origin of DOM. All the results were compared and interpreted to evaluate the environmental quality of Koumoundourou lake and the need for environmental management and protection.

Keywords: anthropogenic contaminant, dissolved organic matter, lake, metal, pollution

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55 Development of Wound Dressing System Based on Hydrogel Matrix Incorporated with pH-Sensitive Nanocarrier-Drug Systems

Authors: Dagmara Malina, Katarzyna Bialik-Wąs, Klaudia Pluta

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The growing significance of transdermal systems, in which skin is a route for systemic drug delivery, has generated a considerable amount of data which has resulted in a deeper understanding of the mechanisms of transport across the skin in the context of the controlled and prolonged release of active substances. One of such solutions may be the use of carrier systems based on intelligent polymers with different physicochemical properties. In these systems, active substances, e.g. drugs, can be conjugated (attached), immobilized, or encapsulated in a polymer matrix that is sensitive to specific environmental conditions (e.g. pH or temperature changes). Intelligent polymers can be divided according to their sensitivity to specific environmental stimuli such as temperature, pH, light, electric, magnetic, sound, or electromagnetic fields. Materials & methods—The first stage of the presented research concerned the synthesis of pH-sensitive polymeric carriers by a radical polymerization reaction. Then, the selected active substance (hydrocortisone) was introduced into polymeric carriers. In a further stage, bio-hybrid sodium alginate/poly(vinyl alcohol) – SA/PVA-based hydrogel matrices modified with various carrier-drug systems were prepared with the chemical cross-linking method. The conducted research included the assessment of physicochemical properties of obtained materials i.e. degree of hydrogel swelling and degradation studies as a function of pH in distilled water and phosphate-buffered saline (PBS) at 37°C in time. The gel fraction represents the insoluble gel fraction as a result of inter-molecule cross-linking formation was also measured. Additionally, the chemical structure of obtained hydrogels was confirmed using FT-IR spectroscopic technique. The dynamic light scattering (DLS) technique was used for the analysis of the average particle size of polymer-carriers and carrier-drug systems. The nanocarriers morphology was observed using SEM microscopy. Results & Discussion—The analysis of the encapsulated polymeric carriers showed that it was possible to obtain the time-stable empty pH-sensitive carrier with an average size 479 nm and the encapsulated system containing hydrocortisone with an average 543 nm, which was introduced into hydrogel structure. Bio-hybrid hydrogel matrices are stable materials, and the presence of an additional component: pH-sensitive carrier – hydrocortisone system, does not reduce the degree of cross-linking of the matrix nor its swelling ability. Moreover, the results of swelling tests indicate that systems containing higher concentrations of the drug have a slightly higher sorption capacity in each of the media used. All analyzed materials show stable and statically changing swelling values in simulated body fluids - there is no sudden fluid uptake and no rapid release from the material. The analysis of FT-IR spectra confirms the chemical structure of the obtained bio-hybrid hydrogel matrices. In the case of modifications with a pH-sensitive carrier, a much more intense band can be observed in the 3200-3500 cm⁻¹ range, which most likely originates from the strong hydrogen interactions that occur between individual components.

Keywords: hydrogels, polymer nanocarriers, sodium alginate/poly(vinyl alcohol) matrices, wound dressings.

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54 A Triple Win: Linking Students, Academics, and External Organisations to Provide Real-World Learning Experiences with Real-World Benefits

Authors: Anne E. Goodenough

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Students often learn best ‘on the job’ through holistic real-world projects. They need real-world experiences to make classroom learning applicable and to increase their employability. Academics typically value working on projects where new knowledge is created and have a genuine desire to help students engage with learning and develop new skills. They might also have institutional pressure to enhance student engagement, retention, and satisfaction. External organizations - especially non-governmental bodies, charities, and small enterprises - often have fundamental and pressing questions, but lack the manpower and academic expertise to answer them effectively. They might also be on the lookout for talented potential employees. This study examines ways in which these diverse requirements can be met simultaneously by creating three-way projects that provide excellent academic and real-world outcomes for all involved. It studied a range of innovative projects across natural sciences (biology, ecology, physical geography and social sciences (human geography, sociology, criminology, and community engagement) to establish how to best harness the potential of this powerful approach. Focal collaborations included: (1) development of practitioner-linked modules; (2) frameworks where students collected/analyzed data for link organizations in research methods modules; (3) placement-based internships and dissertations; and (4) immersive fieldwork projects in novel locations to allow students engage first-hand with contemporary issues as diverse as rhino poaching in South Africa, segregation in Ireland, and gun crime in Florida. Although there was no ‘magic formula’ for success, the approach was found to work best when small projects were developed that were achievable in a short time-frame, both to tie into modular curricula and meet the immediacy expectations of many link organizations. Bigger projects were found to work well in some cases, especially when they were essentially a series of linked smaller projects, either running concurrently or successively with each building on previous work. Opportunities were maximized when there were tangible benefits to the link organization as this generally increased organization investment in the project and motivated students too. The importance of finding the right approach for a given project was found to be key: it was vital to ensure that something that could work effectively as an independent research project for one student, for example, was not shoehorned into being a project for multiple students within a taught module. In general, students were very positive about collaboration projects. They identified benefits to confidence, time-keeping and communication, as well as conveying their enthusiasm when their work was of benefit to the wider community. Several students have gone on to do further work with the link organization in a voluntary capacity or as paid staff, or used the experiences to help them break into the ever-more competitive job market in other ways. Although this approach involves a substantial time investment, especially from academics, the benefits can be profound. The approach has strong potential to engage students, help retention, improve student satisfaction, and teach new skills; keep the knowledge of academics fresh and current; and provide valuable tangible benefits for link organizations: a real triple win.

Keywords: authentic learning, curriculum development, effective education, employability, higher education, innovative pedagogy, link organizations, student experience

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53 A Rare Case of Dissection of Cervical Portion of Internal Carotid Artery, Diagnosed Postpartum

Authors: Bidisha Chatterjee, Sonal Grover, Rekha Gurung

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Postpartum dissection of the internal carotid artery is a relatively rare condition and is considered as an underlying aetiology in 5% to 25% of strokes under the age of 30 to 45 years. However, 86% of these cases recover completely and 14% have mild focal neurological symptoms. Prognosis is generally good with early intervention. The risk quoted for a repeat carotid artery dissection in subsequent pregnancies is less than 2%. 36-year Caucasian primipara presented on postnatal day one of forceps delivery with tachycardia. In the intrapartum period she had a history of prolonged rupture of membranes and developed intrapartum sepsis and was treated with antibiotics. Postpartum ECG showed septal inferior T wave inversion and a troponin level of 19. Subsequently Echocardiogram ruled out post-partum cardiomyopathy. Repeat ECG showed improvement of the previous changes and in the absence of symptoms no intervention was warranted. On day 4 post-delivery, she had developed symptoms of droopy right eyelid, pain around the right eye and itching in the right ear. On examination, she had developed right sided ptosis, unequal pupils (Rt miotic pupil). Cranial nerve examination, reflexes, sensory examination and muscle power was normal. Apart from migraine, there was no medical or family history of note. In view of Horner’s on the right, she had a CT Angiogram and subsequently MR/MRA and was diagnosed with dissection of the cervical portion of the right internal carotid artery. She was discharged on a course of Aspirin 75mg. By 6 week post-natal follow up patient had recovered significantly with occasional episodes of unequal pupils and tingling of right toes which resolved spontaneously. Cervical artery dissection, including VAD and carotid artery dissection, are rare complications of pregnancy with an estimated annual incidence of 2.6–3 per 100,000 pregnancy hospitalizations. Aetiology remains unclear though trauma during straining at labour, underlying arterial disease and preeclampsia have been implicated. Hypercoagulable state during pregnancy and puerperium could also be an important factor. 60-90% cases present with severe headache and neck pain and generally precede neurological symptoms like ipsilateral Horner’s syndrome, retroorbital pain, tinnitus and cranial nerve palsy. Although rare, the consequences of delayed diagnosis and management can lead to severe and permanent neurological deficits. Patients with a strong index of suspicion should undergo an MRI or MRA of head and neck. Antithrombotic and antiplatelet therapy forms the mainstay of therapy with selected cases needing endovascular stenting. Long term prognosis is favourable with either complete resolution or minimal deficit if treatment is prompt. Patients should be counselled about the recurrence risk and possibility of stroke in future pregnancy. Coronary artery dissection is rare and treatable but needs early diagnosis and treatment. Post-partum headache and neck pain with neurological symptoms should prompt urgent imaging followed by antithrombotic and /or antiplatelet therapy. Most cases resolve completely or with minimal sequelae.

Keywords: postpartum, dissection of internal carotid artery, magnetic resonance angiogram, magnetic resonance imaging, antiplatelet, antithrombotic

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52 Chemopreventive Properties of Cannabis sativa L. var. USO31 in Relation to Its Phenolic and Terpenoid Content

Authors: Antonella Di Sotto, Cinzia Ingallina, Caterina Fraschetti, Simone Circi, Marcello Locatelli, Simone Carradori, Gabriela Mazzanti, Luisa Mannina, Silvia Di Giacomo

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Cannabis sativa L. is one of the oldest cultivated plant species known not only for its voluptuous use but also for the wide application in food, textile, and therapeutic industries. Recently, the progress of biotechnologies applied to medicinal plants has allowed to produce different hemp varieties with low content of psychotropic phytoconstituents (tetrahydrocannabinol < 0.2% w/v), thus leading to a renewed industrial and therapeutic interest for this plant. In this context, in order to discover new potential remedies of pharmaceutical and/or nutraceutical interest, the chemopreventive properties of different organic and hydroalcoholic extracts, obtained from the inflorescences of C. sativa L. var. USO31, collected in June and September harvesting, were assessed. Particularly, the antimutagenic activity towards the oxidative DNA-damage induced by tert-butyl hydroperoxide (t-BOOH) was evaluated, and the DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging power of the samples were assessed as possible mechanisms of antimutagenicity. Furthermore, the ability of the extracts to inhibit the glucose-6-phosphate dehydrogenase (G6PD), whose overexpression has been found to play a critical role in neoplastic transformation and tumor progression, has been studied as a possible chemopreventive strategy. A careful phytochemical characterization of the extracts for phenolic and terpenoid composition has been obtained by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods. Under our experimental condition, all the extracts were found able to interfere with the tBOOH-induced mutagenicity in WP2uvrAR strain, although with different potency and effectiveness. The organic extracts from both the harvesting periods were found to be the main effective antimutagenic samples, reaching about a 55% inhibition of the tBOOH-mutagenicity at the highest concentration tested (250 μg/ml). All the extracts exhibited radical scavenger activity against DPPH and ABTS radicals, with a higher potency of the hydroalcoholic samples. The organic extracts were also able to inhibit the G6PD enzyme, being the samples from September harvesting the highly potent (about 50% inhibition respect to the vehicle). At the phytochemical analysis, all the extracts resulted to contain both polar and apolar phenolic compounds. The HPLC analysis revealed the presence of catechin and rutin as the major constituents of the hydroalcoholic extracts, with lower levels of quercetin and ferulic acid. The monoterpene carvacrol was found to be an ubiquitarian constituent. At GC-MS analysis, different terpenoids, among which caryophyllene sesquiterpenes, were identified. This evidence suggests a possible role of both polyphenols and terpenoids in the chemopreventive properties of the extracts from the inflorescences of C. sativa var. USO31. According to the literature, carvacrol and caryophyllene sesquiterpenes can contribute to the strong antimutagenicity although the role of all the hemp phytocomplex cannot be excluded. In conclusion, present results highlight a possible interest for the inflorescences of C. sativa var. USO31 as source of bioactive molecules and stimulate further studies in order to characterize its possible application for nutraceutical and pharmaceutical purposes.

Keywords: antimutagenicity, glucose-6-phosphate dehydrogenase, hemp inflorescences, nutraceuticals, sesquiterpenes

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51 Construction of an Assessment Tool for Early Childhood Development in the World of DiscoveryTM Curriculum

Authors: Divya Palaniappan

Abstract:

Early Childhood assessment tools must measure the quality and the appropriateness of a curriculum with respect to culture and age of the children. Preschool assessment tools lack psychometric properties and were developed to measure only few areas of development such as specific skills in music, art and adaptive behavior. Existing preschool assessment tools in India are predominantly informal and are fraught with judgmental bias of observers. The World of Discovery TM curriculum focuses on accelerating the physical, cognitive, language, social and emotional development of pre-schoolers in India through various activities. The curriculum caters to every child irrespective of their dominant intelligence as per Gardner’s Theory of Multiple Intelligence which concluded "even students as young as four years old present quite distinctive sets and configurations of intelligences". The curriculum introduces a new theme every week where, concepts are explained through various activities so that children with different dominant intelligences could understand it. For example: The ‘Insects’ theme is explained through rhymes, craft and counting corner, and hence children with one of these dominant intelligences: Musical, bodily-kinesthetic and logical-mathematical could grasp the concept. The child’s progress is evaluated using an assessment tool that measures a cluster of inter-dependent developmental areas: physical, cognitive, language, social and emotional development, which for the first time renders a multi-domain approach. The assessment tool is a 5-point rating scale that measures these Developmental aspects: Cognitive, Language, Physical, Social and Emotional. Each activity strengthens one or more of the developmental aspects. During cognitive corner, the child’s perceptual reasoning, pre-math abilities, hand-eye co-ordination and fine motor skills could be observed and evaluated. The tool differs from traditional assessment methodologies by providing a framework that allows teachers to assess a child’s continuous development with respect to specific activities in real time objectively. A pilot study of the tool was done with a sample data of 100 children in the age group 2.5 to 3.5 years. The data was collected over a period of 3 months across 10 centers in Chennai, India, scored by the class teacher once a week. The teachers were trained by psychologists on age-appropriate developmental milestones to minimize observer’s bias. The norms were calculated from the mean and standard deviation of the observed data. The results indicated high internal consistency among parameters and that cognitive development improved with physical development. A significant positive relationship between physical and cognitive development has been observed among children in a study conducted by Sibley and Etnier. In Children, the ‘Comprehension’ ability was found to be greater than ‘Reasoning’ and pre-math abilities as indicated by the preoperational stage of Piaget’s theory of cognitive development. The average scores of various parameters obtained through the tool corroborates the psychological theories on child development, offering strong face validity. The study provides a comprehensive mechanism to assess a child’s development and differentiate high performers from the rest. Based on the average scores, the difficulty level of activities could be increased or decreased to nurture the development of pre-schoolers and also appropriate teaching methodologies could be devised.

Keywords: child development, early childhood assessment, early childhood curriculum, quantitative assessment of preschool curriculum

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50 Impact of Marangoni Stress and Mobile Surface Charge on Electrokinetics of Ionic Liquids Over Hydrophobic Surfaces

Authors: Somnath Bhattacharyya

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The mobile adsorbed surface charge on hydrophobic surfaces can modify the velocity slip condition as well as create a Marangoni stress at the interface. The functionalized hydrophobic walls of micro/nanopores, e.g., graphene nanochannels, may possess physio-sorbed ions. The lateral mobility of the physisorbed absorbed ions creates a friction force as well as an electric force, leading to a modification in the velocity slip condition at the hydrophobic surface. In addition, the non-uniform distribution of these surface ions creates a surface tension gradient, leading to a Marangoni stress. The impact of the mobile surface charge on streaming potential and electrochemical energy conversion efficiency in a pressure-driven flow of ionized liquid through the nanopore is addressed. Also, enhanced electro-osmotic flow through the hydrophobic nanochannel is also analyzed. The mean-filed electrokinetic model is modified to take into account the short-range non-electrostatic steric interactions and the long-range Coulomb correlations. The steric interaction is modeled by considering the ions as charged hard spheres of finite radius suspended in the electrolyte medium. The electrochemical potential is modified by including the volume exclusion effect, which is modeled based on the BMCSL equation of state. The electrostatic correlation is accounted for in the ionic self-energy. The extremal of the self-energy leads to a fourth-order Poisson equation for the electric field. The ion transport is governed by the modified Nernst-Planck equation, which includes the ion steric interactions; born force arises due to the spatial variation of the dielectric permittivity and the dielectrophoretic force on the hydrated ions. This ion transport equation is coupled with the Navier-Stokes equation describing the flow of the ionized fluid and the 3fourth-order Poisson equation for the electric field. We numerically solve the coupled set of nonlinear governing equations along with the prescribed boundary conditions by adopting a control volume approach over a staggered grid arrangement. In the staggered grid arrangements, velocity components are stored on the midpoint of the cell faces to which they are normal, whereas the remaining scalar variables are stored at the center of each cell. The convection and electromigration terms are discretized at each interface of the control volumes using the total variation diminishing (TVD) approach to capture the strong convection resulting from the highly enhanced fluid flow due to the modified model. In order to link pressure to the continuity equation, we adopt a pressure correction-based iterative SIMPLE (Semi-Implicit Method for Pressure-Linked Equations) algorithm, in which the discretized continuity equation is converted to a Poisson equation involving pressure correction terms. Our results show that the physisorbed ions on a hydrophobic surface create an enhanced slip velocity when streaming potential, which enhances the convection current. However, the electroosmotic flow attenuates due to the mobile surface ions.

Keywords: microfluidics, electroosmosis, streaming potential, electrostatic correlation, finite sized ions

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49 Bio-Nanotechnology Approach of Nano-Size Iron Particles as Promising Iron Supplements: An Exploratory Study to Combat the Problems of Iron Fortification in Children and Pregnant Women of Rural India

Authors: Roshni Raha, Kavya P., Gayathri M.

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India, with a humongous population, remains the world's poorest developing nation in terms of nutritional status, with iron deficiency anaemia (IDA) affecting the population. Despite efforts over the past decades, India's anaemia prevalence has not been reduced. Researchers are interested in developing therapies that will minimize the typical side effects of oral iron and optimize iron salts-based treatment through delivery methods based on the physiology of hepcidin regulation. However, they need to come up with iron therapies that will prevent making the infection worse. This article explores using bio-nanotechnology as the alternative, promising substitution of providing iron supplements for the treatment of diarrhoea and gut inflammation in kids and pregnant women. This article is an exploratory study using a literature survey and secondary research from review papers. In the realm of biotechnology, nanoparticles have become extremely famous due to unexpected variations in surface characteristics caused by particle size. Particle size distribution and shape exhibit unusual, enhanced characteristics when reduced to nanoscale. The article attempts to develop a model for a nanotechnology based solution in iron fortification to combat the problems of diarrhoea and gut inflammation. Certain dimensions that have been considered in the model include the size, shape, source, and biosynthesis of the iron nanoparticles. Another area of investigation addressed in the article is the cost-effective biocompatible production of these iron nanoparticles. Studies have demonstrated that a substantial reduction of metal ions to form nanoparticles from the bulk metal occurs in plants because of the presence of a wide diversity of biomolecules. Using this concept, the paper investigates the effectiveness and impact of how similar sources can be used for the biological synthesis of iron nanoparticles. Results showed that iron particles, when prepared in nano-metre size, offer potential advantages. When the particle size of the iron compound decreases and attains nano configuration, its surface area increases, which further improves its solubility in the gastric acid, leading to higher absorption, higher bioavailability, and producing the least organoleptic changes in food. It has no negative effects and possesses a safe, effective profile to reduce IDA. Considering all the parameters, it has been concluded that iron particles in nano configuration serve as alternative iron supplements for the complete treatment of IDA. Nanoparticles of ferric phosphate, ferric pyrophosphate, and iron oxide are the choices of iron supplements. From a sourcing perspective, the paper concludes green sources are the primary sources for the biological synthesis of iron nanoparticles. It will also be a cost-effective strategy since our goal is to treat the target population in rural India. Bio-nanotechnology serves as an alternative and promising substitution for iron supplements due to its low cost, excellent bioavailability, and strong organoleptic properties. One area of future research can be to explore the type of size and shape of iron nanoparticles that would be suitable for the different age groups of pregnant women and children and whether it would be influenced based on the topography in certain areas.

Keywords: anemia, bio-nanotechnology, iron-fortification, nanoparticle

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48 Optimizing Solids Control and Cuttings Dewatering for Water-Powered Percussive Drilling in Mineral Exploration

Authors: S. J. Addinell, A. F. Grabsch, P. D. Fawell, B. Evans

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The Deep Exploration Technologies Cooperative Research Centre (DET CRC) is researching and developing a new coiled tubing based greenfields mineral exploration drilling system utilising down-hole water-powered percussive drill tooling. This new drilling system is aimed at significantly reducing the costs associated with identifying mineral resource deposits beneath deep, barren cover. This system has shown superior rates of penetration in water-rich, hard rock formations at depths exceeding 500 metres. With fluid flow rates of up to 120 litres per minute at 200 bar operating pressure to energise the bottom hole tooling, excessive quantities of high quality drilling fluid (water) would be required for a prolonged drilling campaign. As a result, drilling fluid recovery and recycling has been identified as a necessary option to minimise costs and logistical effort. While the majority of the cuttings report as coarse particles, a significant fines fraction will typically also be present. To maximise tool life longevity, the percussive bottom hole assembly requires high quality fluid with minimal solids loading and any recycled fluid needs to have a solids cut point below 40 microns and a concentration less than 400 ppm before it can be used to reenergise the system. This paper presents experimental results obtained from the research program during laboratory and field testing of the prototype drilling system. A study of the morphological aspects of the cuttings generated during the percussive drilling process shows a strong power law relationship for particle size distributions. This data is critical in optimising solids control strategies and cuttings dewatering techniques. Optimisation of deployable solids control equipment is discussed and how the required centrate clarity was achieved in the presence of pyrite-rich metasediment cuttings. Key results were the successful pre-aggregation of fines through the selection and use of high molecular weight anionic polyacrylamide flocculants and the techniques developed for optimal dosing prior to scroll decanter centrifugation, thus keeping sub 40 micron solids loading within prescribed limits. Experiments on maximising fines capture in the presence of thixotropic drilling fluid additives (e.g. Xanthan gum and other biopolymers) are also discussed. As no core is produced during the drilling process, it is intended that the particle laden returned drilling fluid is used for top-of-hole geochemical and mineralogical assessment. A discussion is therefore presented on the biasing and latency of cuttings representivity by dewatering techniques, as well as the resulting detrimental effects on depth fidelity and accuracy. Data pertaining to the sample biasing with respect to geochemical signatures due to particle size distributions is presented and shows that, depending on the solids control and dewatering techniques used, it can have unwanted influence on top-of-hole analysis. Strategies are proposed to overcome these effects, improving sample quality. Successful solids control and cuttings dewatering for water-powered percussive drilling is presented, contributing towards the successful advancement of coiled tubing based greenfields mineral exploration.

Keywords: cuttings, dewatering, flocculation, percussive drilling, solids control

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47 Targeting Basic Leucine Zipper Transcription Factor ATF-Like Mediated Immune Cells Regulation to Reduce Crohn’s Disease Fistula Incidence

Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

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46 La0.80Ag0.15MnO3 Magnetic Nanoparticles for Self-Controlled Magnetic Fluid Hyperthermia

Authors: Marian Mihalik, Kornel Csach, Martin Kovalik, Matúš Mihalik, Martina Kubovčíková, Maria Zentková, Martin Vavra, Vladimír Girman, Jaroslav Briančin, Marija Perovic, Marija Boškovic, Magdalena Fitta, Robert Pelka

Abstract:

Current nanomaterials for use in biomedicine are based mainly on iron oxides and on present knowledge on magnetic nanostructures. Manganites can represent another material which can be used optionally. Manganites and their unique electronic properties have been extensively studied in the last decades not only due to fundamental interest but to possible applications of colossal magnetoresistance, magnetocaloric effect, and ferroelectric properties. It was found that the oxygen-reduction reaction on perovskite oxide is intimately connected with metal ion e.g., orbital occupation. The effect of oxygen deviation from the stoichiometric composition on crystal structure was studied very carefully by many authors on LaMnO₃. Depending on oxygen content, the crystal structure changes from orthorhombic one to rhombohedric for oxygen content 3.1. In the case of hole-doped manganites, the change from the orthorhombic crystal structure, which is typical for La1-xCaxMnO3 based manganites, to the rhombohedric crystal structure (La1-xMxMnO₃ where M = K, Ag, and Sr based materials) results in an enormous increase of the Curie temperature. In our paper, we study the effect of oxygen content on crystal structure, thermal, and magnetic properties (including magnetocaloric effect) of La1-xAgxMnO₃nano particle system. The content of oxygen in samples was tuned by heat treatment in different thermal regimes and in various environment (air, oxygen, argon). Water nanosuspensions based on La0.80Ag0.15MnO₃ magnetic particles with the Curie temperature of about 43oC were prepared by two different approaches. First, by using a laboratory circulation mill for milling of powder in the presence of sodium dodecyl sulphate (SDS) and subsequent centrifugation. Second nanosuspension was prepared using an agate bowl, etching in citric acid and HNO3, ultrasound homogeniser, centrifugation, and dextran 40 kDA or 15 kDA as surfactant. Electrostatic stabilisation obtained by the first approach did not offer long term kinetic and aggregation colloidal stability and was unable to compensate for attractive forces between particles under a magnetic field. By the second approach, we prepared suspension oversaturated by dextran 40 kDA for steric stabilisation, with evidence of the presence of superparamagnetic behaviour. Low concentration of nanoparticles and not ideal coverage of nanoparticles impacting the stability of ferrofluids was the disadvantage of this approach. Strong steric stabilisation was observable at alcaic conditions under pH = ~10. Application of dextran 15 kDA leads to relatively stable ferrofluid with pH around physiological conditions, but desegregation of powder by HNO₃ was not effective enough, and the average size of fragments was to large of about 150 nm, and we did not see any signature of superparamagnetic behaviour. The prepared ferrofluids were characterised by scanning and transition microscope method, thermogravimetry, magnetization, and AC susceptibility measurements. Specific Absorption Rate measurements were undertaken on powder as well on ferrofluids in order to estimate the potential application of La₀.₈₀Ag₀.₁₅MnO₃ magnetic particles based ferrofluid for hyperthermia. Our complex study contains an investigation of biocompatibility and potential biohazard of this material.

Keywords: manganites, magnetic nanoparticles, oxygen content, magnetic phase transition, magnetocaloric effect, ferrofluid, hyperthermia

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45 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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44 The Influence of Fashion Bloggers on the Pre-Purchase Decision for Online Fashion Products among Generation Y Female Malaysian Consumers

Authors: Mohd Zaimmudin Mohd Zain, Patsy Perry, Lee Quinn

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This study explores how fashion consumers are influenced by fashion bloggers towards pre-purchase decision for online fashion products in a non-Western context. Malaysians rank among the world’s most avid online shoppers, with apparel the third most popular purchase category. However, extant research on fashion blogging focuses on the developed Western market context. Numerous international fashion retailers have entered the Malaysian market from luxury to fast fashion segments of the market; however Malaysian fashion consumers must balance religious and social norms for modesty with their dress style and adoption of fashion trends. Consumers increasingly mix and match Islamic and Western elements of dress to create new styles enabling them to follow Western fashion trends whilst paying respect to social and religious norms. Social media have revolutionised the way that consumers can search for and find information about fashion products. For online fashion brands with no physical presence, social media provide a means of discovery for consumers. By allowing the creation and exchange of user-generated content (UGC) online, they provide a public forum that gives individual consumers their own voices, as well as access to product information that facilitates their purchase decisions. Social media empower consumers and brands have important roles in facilitating conversations among consumers and themselves, to help consumers connect with them and one another. Fashion blogs have become an important fashion information sources. By sharing their personal style and inspiring their followers with what they wear on popular social media platforms such as Instagram, fashion bloggers have become fashion opinion leaders. By creating UGC to spread useful information to their followers, they influence the pre-purchase decision. Hence, successful Western fashion bloggers such as Chiara Ferragni may earn millions of US dollars every year, and some have created their own fashion ranges and beauty products, become judges in fashion reality shows, won awards, and collaborated with high street and luxury brands. As fashion blogging has become more established worldwide, increasing numbers of fashion bloggers have emerged from non-Western backgrounds to promote Islamic fashion styles, such as Hassanah El-Yacoubi and Dian Pelangi. This study adopts a qualitative approach using netnographic content analysis of consumer comments on two famous Malaysian fashion bloggers’ Instagram accounts during January-March 2016 and qualitative interviews with 16 Malaysian Generation Y fashion consumers during September-October 2016. Netnography adapts ethnographic techniques to the study of online communities or computer-mediated communications. Template analysis of the data involved coding comments according to the theoretical framework, which was developed from the literature review. Initial data analysis shows the strong influence of Malaysian fashion bloggers on their followers in terms of lifestyle and morals as well as fashion style. Followers were guided towards the mix and match trend of dress with Western and Islamic elements, for example, showing how vivid colours or accessories could be worked into an outfit whilst still respecting social and religious norms. The blogger’s Instagram account is a form of online community where followers can communicate and gain guidance and support from other followers, as well as from the blogger.

Keywords: fashion bloggers, Malaysia, qualitative, social media

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