Search results for: literacy discovery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1144

Search results for: literacy discovery

34 Novel Aspects of Merger Control Pertaining to Nascent Acquisition: An Analytical Legal Research

Authors: Bhargavi G. Iyer, Ojaswi Bhagat

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It is often noted that the value of a novel idea lies in its successful implementation. However, successful implementation requires the nurturing and encouragement of innovation. Nascent competitors are a true representation of innovation in any given industry. A nascent competitor is an entity whose prospective innovation poses a future threat to an incumbent dominant competitor. While a nascent competitor benefits in several ways, it is also exposed significantly and is at greater risk of facing the brunt of exclusionary practises and abusive conduct by dominant incumbent competitors in the industry. This research paper aims to explore the risks and threats faced by nascent competitors and analyse the benefits they accrue as well as the advantages they proffer to the economy; through an analytical, critical study. In such competitive market environments, a rise of the acquisitions of nascent competitors by the incumbent dominants is observed. Therefore, this paper will examine the dynamics of nascent acquisition. Further, this paper hopes to specifically delve into the role of antitrust bodies in regulating nascent acquisition. This paper also aspires to deal with the question how to distinguish harmful from harmless acquisitions in order to facilitate ideal enforcement practice. This paper proposes mechanisms of scrutiny in order to ensure healthy market practises and efficient merger control in the context of nascent acquisitions. Taking into account the scope and nature of the topic, as well as the resources available and accessible, a combination of the methods of doctrinal research and analytical research were employed, utilising secondary sources in order to assess and analyse the subject of research. While legally evaluating the Killer Acquisition theory and the Nascent Potential Acquisition theory, this paper seeks to critically survey the precedents and instances of nascent acquisitions. In addition to affording a compendious account of the legislative framework and regulatory mechanisms in the United States, the United Kingdom, and the European Union; it hopes to suggest an internationally practicable legal foundation for domestic legislation and enforcement to adopt. This paper hopes to appreciate the complexities and uncertainties with respect to nascent acquisitions and attempts to suggest viable and plausible policy measures in antitrust law. It additionally attempts to examine the effects of such nascent acquisitions upon the consumer and the market economy. This paper weighs the argument of shifting the evidentiary burden on to the merging parties in order to improve merger control and regulation and expounds on its discovery of the strengths and weaknesses of the approach. It is posited that an effective combination of factual, legal, and economic analysis of both the acquired and acquiring companies possesses the potential to improve ex post and ex ante merger review outcomes involving nascent companies; thus, preventing anti-competitive practises. This paper concludes with an analysis of the possibility and feasibility of industry-specific identification of anti-competitive nascent acquisitions and implementation of measures accordingly.

Keywords: acquisition, antitrust law, exclusionary practises merger control, nascent competitor

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33 Design and Implementation of an Affordable Electronic Medical Records in a Rural Healthcare Setting: A Qualitative Intrinsic Phenomenon Case Study

Authors: Nitika Sharma, Yogesh Jain

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Introduction: An efficient Information System helps in improving the service delivery as well provides the foundation for policy and regulation of other building blocks of Health System. Health care organizations require an integrated working of its various sub-systems. An efficient EMR software boosts the teamwork amongst the various sub-systems thereby resulting in improved service delivery. Although there has been a huge impetus to EMR under the Digital India initiative, it has still not been mandated in India. It is generally implemented in huge funded public or private healthcare organizations only. Objective: The study was conducted to understand the factors that lead to the successful adoption of an affordable EMR in the low level healthcare organization. It intended to understand the design of the EMR and address the solutions to the challenges faced in adoption of the EMR. Methodology: The study was conducted in a non-profit registered Healthcare organization that has been providing healthcare facilities to more than 2500 villages including certain areas that are difficult to access. The data was collected with help of field notes, in-depth interviews and participant observation. A total of 16 participants using the EMR from different departments were enrolled via purposive sampling technique. The participants included in the study were working in the organization before the implementation of the EMR system. The study was conducted in one month period from 25 June-20 July 2018. The Ethical approval was taken from the institute along with prior approval of the participants. Data analysis: A word document of more than 4000 words was obtained after transcribing and translating the answers of respondents. It was further analyzed by focused coding, a line by line review of the transcripts, underlining words, phrases or sentences that might suggest themes to do thematic narrative analysis. Results: Based on the answers the results were thematically grouped under four headings: 1. governance of organization, 2. architecture and design of the software, 3. features of the software, 4. challenges faced in adoption and the solutions to address them. It was inferred that the successful implementation was attributed to the easy and comprehensive design of the system which has facilitated not only easy data storage and retrieval but contributes in constructing a decision support system for the staff. Portability has lead to increased acceptance by physicians. The proper division of labor, increased efficiency of staff, incorporation of auto-correction features and facilitation of task shifting has lead to increased acceptance amongst the users of various departments. Geographical inhibitions, low computer literacy and high patient load were the major challenges faced during its implementation. Despite of dual efforts made both by the architects and administrators to combat these challenges, there are still certain ongoing challenges faced by organization. Conclusion: Whenever any new technology is adopted there are certain innovators, early adopters, late adopters and laggards. The same pattern was followed in adoption of this software. He challenges were overcome with joint efforts of organization administrators and users as well. Thereby this case study provides a framework of implementing similar systems in public sector of countries that are struggling for digitizing the healthcare in presence of crunch of human and financial resources.

Keywords: EMR, healthcare technology, e-health, EHR

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32 Web-Based Decision Support Systems and Intelligent Decision-Making: A Systematic Analysis

Authors: Serhat Tüzün, Tufan Demirel

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Decision Support Systems (DSS) have been investigated by researchers and technologists for more than 35 years. This paper analyses the developments in the architecture and software of these systems, provides a systematic analysis for different Web-based DSS approaches and Intelligent Decision-making Technologies (IDT), with the suggestion for future studies. Decision Support Systems literature begins with building model-oriented DSS in the late 1960s, theory developments in the 1970s, and the implementation of financial planning systems and Group DSS in the early and mid-80s. Then it documents the origins of Executive Information Systems, online analytic processing (OLAP) and Business Intelligence. The implementation of Web-based DSS occurred in the mid-1990s. With the beginning of the new millennia, intelligence is the main focus on DSS studies. Web-based technologies are having a major impact on design, development and implementation processes for all types of DSS. Web technologies are being utilized for the development of DSS tools by leading developers of decision support technologies. Major companies are encouraging its customers to port their DSS applications, such as data mining, customer relationship management (CRM) and OLAP systems, to a web-based environment. Similarly, real-time data fed from manufacturing plants are now helping floor managers make decisions regarding production adjustment to ensure that high-quality products are produced and delivered. Web-based DSS are being employed by organizations as decision aids for employees as well as customers. A common usage of Web-based DSS has been to assist customers configure product and service according to their needs. These systems allow individual customers to design their own products by choosing from a menu of attributes, components, prices and delivery options. The Intelligent Decision-making Technologies (IDT) domain is a fast growing area of research that integrates various aspects of computer science and information systems. This includes intelligent systems, intelligent technology, intelligent agents, artificial intelligence, fuzzy logic, neural networks, machine learning, knowledge discovery, computational intelligence, data science, big data analytics, inference engines, recommender systems or engines, and a variety of related disciplines. Innovative applications that emerge using IDT often have a significant impact on decision-making processes in government, industry, business, and academia in general. This is particularly pronounced in finance, accounting, healthcare, computer networks, real-time safety monitoring and crisis response systems. Similarly, IDT is commonly used in military decision-making systems, security, marketing, stock market prediction, and robotics. Even though lots of research studies have been conducted on Decision Support Systems, a systematic analysis on the subject is still missing. Because of this necessity, this paper has been prepared to search recent articles about the DSS. The literature has been deeply reviewed and by classifying previous studies according to their preferences, taxonomy for DSS has been prepared. With the aid of the taxonomic review and the recent developments over the subject, this study aims to analyze the future trends in decision support systems.

Keywords: decision support systems, intelligent decision-making, systematic analysis, taxonomic review

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31 Entrepreneurial Venture Creation through Anchor Event Activities: Pop-Up Stores as On-Site Arenas

Authors: Birgit A. A. Solem, Kristin Bentsen

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

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

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30 Centrality and Patent Impact: Coupled Network Analysis of Artificial Intelligence Patents Based on Co-Cited Scientific Papers

Authors: Xingyu Gao, Qiang Wu, Yuanyuan Liu, Yue Yang

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In the era of the knowledge economy, the relationship between scientific knowledge and patents has garnered significant attention. Understanding the intricate interplay between the foundations of science and technological innovation has emerged as a pivotal challenge for both researchers and policymakers. This study establishes a coupled network of artificial intelligence patents based on co-cited scientific papers. Leveraging centrality metrics from network analysis offers a fresh perspective on understanding the influence of information flow and knowledge sharing within the network on patent impact. The study initially obtained patent numbers for 446,890 granted US AI patents from the United States Patent and Trademark Office’s artificial intelligence patent database for the years 2002-2020. Subsequently, specific information regarding these patents was acquired using the Lens patent retrieval platform. Additionally, a search and deduplication process was performed on scientific non-patent references (SNPRs) using the Web of Science database, resulting in the selection of 184,603 patents that cited 37,467 unique SNPRs. Finally, this study constructs a coupled network comprising 59,379 artificial intelligence patents by utilizing scientific papers co-cited in patent backward citations. In this network, nodes represent patents, and if patents reference the same scientific papers, connections are established between them, serving as edges within the network. Nodes and edges collectively constitute the patent coupling network. Structural characteristics such as node degree centrality, betweenness centrality, and closeness centrality are employed to assess the scientific connections between patents, while citation count is utilized as a quantitative metric for patent influence. Finally, a negative binomial model is employed to test the nonlinear relationship between these network structural features and patent influence. The research findings indicate that network structural features such as node degree centrality, betweenness centrality, and closeness centrality exhibit inverted U-shaped relationships with patent influence. Specifically, as these centrality metrics increase, patent influence initially shows an upward trend, but once these features reach a certain threshold, patent influence starts to decline. This discovery suggests that moderate network centrality is beneficial for enhancing patent influence, while excessively high centrality may have a detrimental effect on patent influence. This finding offers crucial insights for policymakers, emphasizing the importance of encouraging moderate knowledge flow and sharing to promote innovation when formulating technology policies. It suggests that in certain situations, data sharing and integration can contribute to innovation. Consequently, policymakers can take measures to promote data-sharing policies, such as open data initiatives, to facilitate the flow of knowledge and the generation of innovation. Additionally, governments and relevant agencies can achieve broader knowledge dissemination by supporting collaborative research projects, adjusting intellectual property policies to enhance flexibility, or nurturing technology entrepreneurship ecosystems.

Keywords: centrality, patent coupling network, patent influence, social network analysis

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29 Culture and Health Equity: Unpacking the Sociocultural Determinants of Eye Health for Indigenous Australian Diabetics

Authors: Aryati Yashadhana, Ted Fields Jnr., Wendy Fernando, Kelvin Brown, Godfrey Blitner, Francis Hayes, Ruby Stanley, Brian Donnelly, Bridgette Jerrard, Anthea Burnett, Anthony B. Zwi

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Indigenous Australians experience some of the worst health outcomes globally, with life expectancy being significantly poorer than those of non-Indigenous Australians. This is largely attributed to preventable diseases such as diabetes (prevalence 39% in Indigenous Australian adults > 55 years), which is attributed to a raised risk of diabetic visual impairment and cataract among Indigenous adults. Our study aims to explore the interface between structural and sociocultural determinants and human agency, in order to understand how they impact (1) accessibility of eye health and chronic disease services and (2) the potential for Indigenous patients to achieve positive clinical eye health outcomes. We used Participatory Action Research methods, and aimed to privilege the voices of Indigenous people through community collaboration. Semi-structured interviews (n=82) and patient focus groups (n=8) were conducted by Indigenous Community-Based Researchers (CBRs) with diabetic Indigenous adults (> 40 years) in four remote communities in Australia. Interviews (n=25) and focus groups (n=4) with primary health care clinicians in each community were also conducted. Data were audio recorded, transcribed verbatim, and analysed thematically using grounded theory, comparative analysis and Nvivo 10. Preliminary analysis occurred in tandem with data collection to determine theoretical saturation. The principal investigator (AY) led analysis sessions with CBRs, fostering cultural and contextual appropriateness to interpreting responses, knowledge exchange and capacity building. Identified themes were conceptualised into three spheres of influence: structural (health services, government), sociocultural (Indigenous cultural values, distrust of the health system, ongoing effects of colonialism and dispossession) and individual (health beliefs/perceptions, patient phenomenology). Permeating these spheres of influence were three core determinants: economic disadvantage, health literacy/education, and cultural marginalisation. These core determinants affected accessibility of services, and the potential for patients to achieve positive clinical outcomes at every level of care (primary, secondary, tertiary). Our findings highlight the clinical realities of institutionalised and structural inequities, illustrated through the lived experiences of Indigenous patients and primary care clinicians in the four sampled communities. The complex determinants surrounding inequity in health for Indigenous Australians, are entrenched through a longstanding experience of cultural discrimination and ostracism. Secure and long term funding of Aboriginal Community Controlled Health Services will be valuable, but are insufficient to address issues of inequity. Rather, working collaboratively with communities to build trust, and identify needs and solutions at the grassroots level, while leveraging community voices to drive change at the systemic/policy level are recommended.

Keywords: indigenous, Australia, culture, public health, eye health, diabetes, social determinants of health, sociology, anthropology, health equity, aboriginal and Torres strait islander, primary care

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28 Integrating Data Mining within a Strategic Knowledge Management Framework: A Platform for Sustainable Competitive Advantage within the Australian Minerals and Metals Mining Sector

Authors: Sanaz Moayer, Fang Huang, Scott Gardner

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In the highly leveraged business world of today, an organisation’s success depends on how it can manage and organize its traditional and intangible assets. In the knowledge-based economy, knowledge as a valuable asset gives enduring capability to firms competing in rapidly shifting global markets. It can be argued that ability to create unique knowledge assets by configuring ICT and human capabilities, will be a defining factor for international competitive advantage in the mid-21st century. The concept of KM is recognized in the strategy literature, and increasingly by senior decision-makers (particularly in large firms which can achieve scalable benefits), as an important vehicle for stimulating innovation and organisational performance in the knowledge economy. This thinking has been evident in professional services and other knowledge intensive industries for over a decade. It highlights the importance of social capital and the value of the intellectual capital embedded in social and professional networks, complementing the traditional focus on creation of intellectual property assets. Despite the growing interest in KM within professional services there has been limited discussion in relation to multinational resource based industries such as mining and petroleum where the focus has been principally on global portfolio optimization with economies of scale, process efficiencies and cost reduction. The Australian minerals and metals mining industry, although traditionally viewed as capital intensive, employs a significant number of knowledge workers notably- engineers, geologists, highly skilled technicians, legal, finance, accounting, ICT and contracts specialists working in projects or functions, representing potential knowledge silos within the organisation. This silo effect arguably inhibits knowledge sharing and retention by disaggregating corporate memory, with increased operational and project continuity risk. It also may limit the potential for process, product, and service innovation. In this paper the strategic application of knowledge management incorporating contemporary ICT platforms and data mining practices is explored as an important enabler for knowledge discovery, reduction of risk, and retention of corporate knowledge in resource based industries. With reference to the relevant strategy, management, and information systems literature, this paper highlights possible connections (currently undergoing empirical testing), between an Strategic Knowledge Management (SKM) framework incorporating supportive Data Mining (DM) practices and competitive advantage for multinational firms operating within the Australian resource sector. We also propose based on a review of the relevant literature that more effective management of soft and hard systems knowledge is crucial for major Australian firms in all sectors seeking to improve organisational performance through the human and technological capability captured in organisational networks.

Keywords: competitive advantage, data mining, mining organisation, strategic knowledge management

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27 Role of Functional Divergence in Specific Inhibitor Design: Using γ-Glutamyltranspeptidase (GGT) as a Model Protein

Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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26 Transformers in Gene Expression-Based Classification

Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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25 Decrease in Olfactory Cortex Volume and Alterations in Caspase Expression in the Olfactory Bulb in the Pathogenesis of Alzheimer’s Disease

Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

Abstract:

Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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24 Differential Expression Analysis of Busseola fusca Larval Transcriptome in Response to Cry1Ab Toxin Challenge

Authors: Bianca Peterson, Tomasz J. Sańko, Carlos C. Bezuidenhout, Johnnie Van Den Berg

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Busseola fusca (Fuller) (Lepidoptera: Noctuidae), the maize stem borer, is a major pest in sub-Saharan Africa. It causes economic damage to maize and sorghum crops and has evolved non-recessive resistance to genetically modified (GM) maize expressing the Cry1Ab insecticidal toxin. Since B. fusca is a non-model organism, very little genomic information is publicly available, and is limited to some cytochrome c oxidase I, cytochrome b, and microsatellite data. The biology of B. fusca is well-described, but still poorly understood. This, in combination with its larval-specific behavior, may pose problems for limiting the spread of current resistant B. fusca populations or preventing resistance evolution in other susceptible populations. As part of on-going research into resistance evolution, B. fusca larvae were collected from Bt and non-Bt maize in South Africa, followed by RNA isolation (15 specimens) and sequencing on the Illumina HiSeq 2500 platform. Quality of reads was assessed with FastQC, after which Trimmomatic was used to trim adapters and remove low quality, short reads. Trinity was used for the de novo assembly, whereas TransRate was used for assembly quality assessment. Transcript identification employed BLAST (BLASTn, BLASTp, and tBLASTx comparisons), for which two libraries (nucleotide and protein) were created from 3.27 million lepidopteran sequences. Several transcripts that have previously been implicated in Cry toxin resistance was identified for B. fusca. These included aminopeptidase N, cadherin, alkaline phosphatase, ATP-binding cassette transporter proteins, and mitogen-activated protein kinase. MEGA7 was used to align these transcripts to reference sequences from Lepidoptera to detect mutations that might potentially be contributing to Cry toxin resistance in this pest. RSEM and Bioconductor were used to perform differential gene expression analysis on groups of B. fusca larvae challenged and unchallenged with the Cry1Ab toxin. Pairwise expression comparisons of transcripts that were at least 16-fold expressed at a false-discovery corrected statistical significance (p) ≤ 0.001 were extracted and visualized in a hierarchically clustered heatmap using R. A total of 329,194 transcripts with an N50 of 1,019 bp were generated from the over 167.5 million high-quality paired-end reads. Furthermore, 110 transcripts were over 10 kbp long, of which the largest one was 29,395 bp. BLAST comparisons resulted in identification of 157,099 (47.72%) transcripts, among which only 3,718 (2.37%) were identified as Cry toxin receptors from lepidopteran insects. According to transcript expression profiles, transcripts were grouped into three subclusters according to the similarity of their expression patterns. Several immune-related transcripts (pathogen recognition receptors, antimicrobial peptides, and inhibitors) were up-regulated in the larvae feeding on Bt maize, indicating an enhanced immune status in response to toxin exposure. Above all, extremely up-regulated arylphorin genes suggest that enhanced epithelial healing is one of the resistance mechanisms employed by B. fusca larvae against the Cry1Ab toxin. This study is the first to provide a resource base and some insights into a potential mechanism of Cry1Ab toxin resistance in B. fusca. Transcriptomic data generated in this study allows identification of genes that can be targeted by biotechnological improvements of GM crops.

Keywords: epithelial healing, Lepidoptera, resistance, transcriptome

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23 Policies for Circular Bioeconomy in Portugal: Barriers and Constraints

Authors: Ana Fonseca, Ana Gouveia, Edgar Ramalho, Rita Henriques, Filipa Figueiredo, João Nunes

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Due to persistent climate pressures, there is a need to find a resilient economic system that is regenerative in nature. Bioeconomy offers the possibility of replacing non-renewable and non-biodegradable materials derived from fossil fuels with ones that are renewable and biodegradable, while a Circular Economy aims at sustainable and resource-efficient operations. The term "Circular Bioeconomy", which can be summarized as all activities that transform biomass for its use in various product streams, expresses the interaction between these two ideas. Portugal has a very favourable context to promote a Circular Bioeconomy due to its variety of climates and ecosystems, availability of biologically based resources, location, and geomorphology. Recently, there have been political and legislative efforts to develop the Portuguese Circular Bioeconomy. The Action Plan for a Sustainable Bioeconomy, approved in 2021, is composed of five axes of intervention, ranging from sustainable production and the use of regionally based biological resources to the development of a circular and sustainable bioindustry through research and innovation. However, as some statistics show, Portugal is still far from achieving circularity. According to Eurostat, Portugal has circularity rates of 2.8%, which is the second lowest among the member states of the European Union. Some challenges contribute to this scenario, including sectorial heterogeneity and fragmentation, prevalence of small producers, lack of attractiveness for younger generations, and absence of implementation of collaborative solutions amongst producers and along value chains.Regarding the Portuguese industrial sector, there is a tendency towards complex bureaucratic processes, which leads to economic and financial obstacles and an unclear national strategy. Together with the limited number of incentives the country has to offer to those that pretend to abandon the linear economic model, many entrepreneurs are hesitant to invest the capital needed to make their companies more circular. Absence of disaggregated, georeferenced, and reliable information regarding the actual availability of biological resources is also a major issue. Low literacy on bioeconomy among many of the sectoral agents and in society in general directly impacts the decisions of production and final consumption. The WinBio project seeks to outline a strategic approach for the management of weaknesses/opportunities in the technology transfer process, given the reality of the territory, through road mapping and national and international benchmarking. The developed work included the identification and analysis of agents in the interior region of Portugal, natural endogenous resources, products, and processes associated with potential development. Specific flow of biological wastes, possible value chains, and the potential for replacing critical raw materials with bio-based products was accessed, taking into consideration other countries with a matured bioeconomy. The study found food industry, agriculture, forestry, and fisheries generate huge amounts of waste streams, which in turn provide an opportunity for the establishment of local bio-industries powered by this biomass. The project identified biological resources with potential for replication and applicability in the Portuguese context. The richness of natural resources and potentials known in the interior region of Portugal is a major key to developing the Circular Economy and sustainability of the country.

Keywords: circular bioeconomy, interior region of portugal, regional development., public policy

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22 Creating a Critical Digital Pedagogy Context: Challenges and Potential of Designing and Implementing a Blended Learning Intervention for Adult Refugees in Greece

Authors: Roula Kitsiou, Sofia Tsioli, Eleni Gana

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The current sociopolitical realities (displacement, encampment, and resettlement) refugees experience in Greece are a quite complex issue. Their educational and social ‘integration’ is characterized by transition, insecurity, and constantly changing needs. Based on the current research data, technology and more specifically mobile phones are one of the most important resources for refugees, regardless of their levels of conventional literacy. The proposed paper discusses the challenges encountered during the design and implementation of the educational Action 16 ‘Language Education for Adult Refugees’. Action 16 is one of the 24 Actions of the Project PRESS (Provision of Refugee Education and Support Scheme), funded by the Hellenic Open University (2016-2017). Project PRESS had two main objectives: a) to address the educational and integration needs of refugees in transit, who currently reside in Greece, and b) implement research-based educational interventions in online and offline sites. In the present paper, the focus is on reflection and discussion about the challenges and the potential of integrating technology in language learning for a target-group with many specific needs, which have been recorded in field notes among other research tools (ethnographic data) used in the context of PRESS. Action 16, explores if and how technology enhanced language activities in real-time and place mediated through teachers, as well as an autonomous computer-mediated learning space (moodle platform and application) builds on and expands the linguistic, cultural and digital resources and repertoires of the students by creating collaborative face-to-face and digital learning spaces. A broader view on language as a dynamic puzzle of semiotic resources and processes based on the concept of translanguaging is adopted. Specifically, designing the blended learning environment we draw on the construct of translanguaging a) as a symbolic means to valorize students’ repertoires and practices, b) as a method to reach to specific applications of a target-language that the context brings forward (Greek useful to them), and c) as a means to expand refugees’ repertoires. This has led to the creation of a learning space where students' linguistic and cultural resources can find paths to expression. In this context, communication and learning are realized by mutually investing multiple aspects of the team members' identities as educational material designers, teachers, and students on the teaching and learning processes. Therefore, creativity, humour, code-switching, translation, transference etc. are all possible means that can be employed in order to promote multilingual communication and language learning towards raising intercultural awareness in a critical digital pedagogy context. The qualitative analysis includes critical reflection on the developed educational material, team-based reflexive discussions, teachers’ reports data, and photographs from the interventions. The endeavor to involve women and men with a refugee background into a blended learning experience was quite innovative especially for the Greek context. It reflects a pragmatist ethos of the choices made in order to respond to the here-and-now needs of the refugees, and finally it was a very challenging task that has led all actors involved into Action 16 to (re)negotiations of subjectivities and products in a creative and hopeful way.

Keywords: blended learning, integration, language education, refugees

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21 Awareness Creation of Benefits of Antitrypsin-Free Nutraceutical Biopowder for Increasing Human Serum Albumin Synthesis as Possible Adjunct for Management of MDRTB or MDRTB-HIV Patients

Authors: Vincent Oghenekevbe Olughor, Olusoji Mayowa Ige

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Except for a preexisting liver disease and malnutrition, there are no predilections for low serum albumin (SA) levels in humans. At normal reference levels (4.0-6.0g/dl) SA is a universal marker for mortality and morbidity risks assessments where depletion by 1.0g/dl increases mortality risk by 137% and morbidity by 89%.It has 40 known functions contributing significantly to the sustenance of human life. A depletion in SA to <2.2g/dl, in most clinical settings worldwide, leads to loss of oncotic pressure of blood causing clinical manifestations of bipedal Oedema, in which the patients remain conscious. SA also contributes significantly to buffering of blood to a life-sustaining pH of 7.35-7.45. A drop in blood pH to <6.9 will lead to instant coma and death, which can occur after SA continues to deplete after manifestations of bipedal Oedema. In an intervention study conducted in 2014 following the discovery that “SA is depleted during malaria fever”, a Nutraceutical formulated for use as treatment adjunct to prevent SA depletions during malaria to <2.4g/dl after Efficacy testing was found to be satisfactory. There are five known types of Malaria caused by Apicomplexan parasites, Plasmodium: the most lethal being that caused by Plasmodium falciparum causing malignant tertian malaria, in which the fever was occurring every 48 hours coincides with the dumping of malaria-toxins (Hemozoin) into blood, causing contamination: blood must remain sterile. Other Apicomplexan parasites, Toxoplasma and Cryptosporidium, are opportunistic infections of HIV. Separate studies showed SA depletions in MDRTB (multidrug resistant TB), and MDRTB-HIV patients by the same mechanism discovered with malaria and such depletions will be further complicated whenever Apicomplexan parasitic infections co-exist. Both Apicomplexan parasites and the TB parasite belong to the Obligate-group of Parasites, which are parasites that replicate only inside its host; and most of them have capacities to over-consume host nutrients during parasitaemia. In MDRTB patients the body attempts repeatedly to prevent depletions in SA to critical levels in the presence of adequate nutrients and only for a while in MDRTB-HIV patients. These groups of patients will, therefore, benefit from the already tested Nutraceutical in malaria patients. The Nutraceutical bio-Powder was formulated (to BP 1988 specification) from twelve nature-based food-grade nutrients containing all dedicated nutrients for ensuring improved synthesis of Albumin by the liver. The Nutraceutical was administered daily for 38±2days in 23 children, in a prospective phase-2 clinical trial, and its impact on body weight and core blood parameters were documented at the start and end of efficacy testing period. Sixteen children who did not experience malaria-induced depletions of SA had significant SA increase; seven children who experienced malaria-induced depletions of SA had insignificant SA decrease. The Packed Cell Volume Percentage (PCV %), a measure of the Oxygen carrying capacity of blood and the amount of nutrients the body can absorb, increased in both groups. The total serum proteins (SA+ Globulins) increased or decreased within the continuum of normal. In conclusion, MDRTB and MDRTB-HIV patients will benefit from a variant of this Nutraceutical when used as treatment adjunct.

Keywords: antitrypsin-free Nutraceutical, apicomplexan parasites, no predilections for low serum albumin, toxoplasmosis

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20 On the Utility of Bidirectional Transformers in Gene Expression-Based Classification

Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of the flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on the spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts, as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with an attention mechanism. In previous works on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work, with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on the presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: machine learning, classification and regression, gene circuit design, bidirectional transformers

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19 A Postmodern Framework for Quranic Hermeneutics

Authors: Christiane Paulus

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Post-Islamism assumes that the Quran should not be viewed in terms of what Lyotard identifies as a ‘meta-narrative'. However, its socio-ethical content can be viewed as critical of power discourse (Foucault). Practicing religion seems to be limited to rites and individual spirituality, taqwa. Alternatively, can we build on Muhammad Abduh's classic-modern reform and develop it through a postmodernist frame? This is the main question of this study. Through his general and vague remarks on the context of the Quran, Abduh was the first to refer to the historical and cultural distance of the text as an obstacle for interpretation. His application, however, corresponded to the modern absolute idea of authentic sharia. He was followed by Amin al-Khuli, who hermeneutically linked the content of the Quran to the theory of evolution. Fazlur Rahman and Nasr Hamid abu Zeid remain reluctant to go beyond the general level in terms of context. The hermeneutic circle, therefore, persists in challenging, how to get out to overcome one’s own assumptions. The insight into and the acceptance of the lasting ambivalence of understanding can be grasped as a postmodern approach; it is documented in Derrida's discovery of the shift in text meanings, difference, also in Lyotard's theory of différend. The resulting mixture of meanings (Wolfgang Welsch) can be read together with the classic ambiguity of the premodern interpreters of the Quran (Thomas Bauer). Confronting hermeneutic difficulties in general, Niklas Luhmann proves every description an attribution, tautology, i.e., remaining in the circle. ‘De-tautologization’ is possible, namely by analyzing the distinctions in the sense of objective, temporal and social information that every text contains. This could be expanded with the Kantian aesthetic dimension of reason (critique of pure judgment) corresponding to the iʽgaz of the Coran. Luhmann asks, ‘What distinction does the observer/author make?’ Quran as a speech from God to the first listeners could be seen as a discourse responding to the problems of everyday life of that time, which can be viewed as the general goal of the entire Qoran. Through reconstructing koranic Lifeworlds (Alfred Schütz) in detail, the social structure crystallizes the socio-economic differences, the enormous poverty. The koranic instruction to provide the basic needs for the neglected groups, which often intersect (old, poor, slaves, women, children), can be seen immediately in the text. First, the references to lifeworlds/social problems and discourses in longer koranic passages should be hypothesized. Subsequently, information from the classic commentaries could be extracted, the classical Tafseer, in particular, contains rich narrative material for reconstructing. By selecting and assigning suitable, specific context information, the meaning of the description becomes condensed (Clifford Geertz). In this manner, the text gets necessarily an alienation and is newly accessible. The socio-ethical implications can thus be grasped from the difference of the original problem and the revealed/improved order/procedure; this small step can be materialized as such, not as an absolute solution but as offering plausible patterns for today’s challenges as the Agenda 2030.

Keywords: postmodern hermeneutics, condensed description, sociological approach, small steps of reform

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18 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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17 Broad Host Range Bacteriophage Cocktail for Reduction of Staphylococcus aureus as Potential Therapy for Atopic Dermatitis

Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

Abstract:

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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16 Association between Polygenic Risk of Alzheimer's Dementia, Brain MRI and Cognition in UK Biobank

Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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15 Single Crystal Growth in Floating-Zone Method and Properties of Spin Ladders: Quantum Magnets

Authors: Rabindranath Bag, Surjeet Singh

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Materials in which the electrons are strongly correlated provide some of the most challenging and exciting problems in condensed matter physics today. After the discovery of high critical temperature superconductivity in layered or two-dimensional copper oxides, many physicists got attention in cuprates and it led to an upsurge of interest in the synthesis and physical properties of copper-oxide based material. The quest to understand superconducting mechanism in high-temperature cuprates, drew physicist’s attention to somewhat simpler compounds consisting of spin-chains or one-dimensional lattice of coupled spins. Low-dimensional quantum magnets are of huge contemporary interest in basic sciences as well emerging technologies such as quantum computing and quantum information theory, and heat management in microelectronic devices. Spin ladder is an example of quasi one-dimensional quantum magnets which provides a bridge between one and two dimensional materials. One of the examples of quasi one-dimensional spin-ladder compounds is Sr14Cu24O41, which exhibits a lot of interesting and exciting physical phenomena in low dimensional systems. Very recently, the ladder compound Sr14Cu24O41 was shown to exhibit long-distance quantum entanglement crucial to quantum information theory. Also, it is well known that hole-compensation in this material results in very high (metal-like) anisotropic thermal conductivity at room temperature. These observations suggest that Sr14Cu24O41 is a potential multifunctional material which invites further detailed investigations. To investigate these properties one must needs a large and high quality of single crystal. But these systems are showing incongruently melting behavior, which brings many difficulties to grow a large and quality of single crystals. Hence, we are using TSFZ (Travelling Solvent Floating Zone) method to grow the high quality of single crystals of the low dimensional magnets. Apart from this, it has unique crystal structure (alternating stacks of plane containing edge-sharing CuO2 chains, and the plane containing two-leg Cu2O3 ladder with intermediate Sr layers along the b- axis), which is also incommensurate in nature. It exhibits abundant physical phenomenon such as spin dimerization, crystallization of charge holes and charge density wave. The maximum focus of research so far involved in introducing defects on A-site (Sr). However, apart from the A-site (Sr) doping, there are only few studies in which the B-site (Cu) doping of polycrystalline Sr14Cu24O41 have been discussed and the reason behind this is the possibility of two doping sites for Cu (CuO2 chain and Cu2O3 ladder). Therefore, in our present work, the crystals (pristine and Cu-site doped) were grown by using TSFZ method by tuning the growth parameters. The Laue diffraction images, optical polarized microscopy and Scanning Electron Microscopy (SEM) images confirm the quality of the grown crystals. Here, we report the single crystal growth, magnetic and transport properties of Sr14Cu24O41 and its lightly doped variants (magnetic and non-magnetic) containing less than 1% of Co, Ni, Al and Zn impurities. Since, any real system will have some amount of weak disorder, our studies on these ladder compounds with controlled dilute disorder would be significant in the present context.

Keywords: low-dimensional quantum magnets, single crystal, spin-ladder, TSFZ technique

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14 Developing Pan-University Collaborative Initiatives in Support of Diversity and Inclusive Campuses

Authors: David Philpott, Karen Kennedy

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In recognition of an increasingly diverse student population, a Teaching and Learning Framework was developed at Memorial University of Newfoundland. This framework emphasizes work that is engaging, supportive, inclusive, responsive, committed to discovery, and is outcomes-oriented for both educators and learners. The goal of the Teaching and Learning framework was to develop a number of initiatives that builds on existing knowledge, proven programs, and existing supports in order to respond to the specific needs of identified groups of diverse learners: 1) academically vulnerable first year students; 2) students with individual learning needs associated with disorders and/or mental health issues; 3) international students and those from non-western cultures. This session provides an overview of this process. The strategies employed to develop these initiatives were drawn primarily from research on student success and retention (literature review), information on pre-existing programs (environmental scan), an analysis of in-house data on students at our institution; consultations with key informants at all of Memorial’s campuses. The first initiative that emerged from this research was a pilot project proposal for a first-year success program in support of the first-year experience of academically vulnerable students. This program offers a university experience that is enhanced by smaller classes, supplemental instruction, learning communities, and advising sessions. The second initiative that arose under the mandate of the Teaching and Learning Framework was a collaborative effort between two institutions (Memorial University and the College of the North Atlantic). Both institutions participated in a shared conversation to examine programs and services that support an accessible and inclusive environment for students with disorders and/or mental health issues. A report was prepared based on these conversations and an extensive review of research and programs across the country. Efforts are now being made to explore possible initiatives that address culturally diverse and non-traditional learners. While an expanding literature has emerged on diversity in higher education, the process of developing institutional initiatives is usually excluded from such discussions, while the focus remains on effective practice. The proposals that were developed constitute a co-ordination and strengthening of existing services and programs; a weaving of supports to engage a diverse body of students in a sense of community. This presentation will act as a guide through the process of developing projects addressing learner diversity and engage attendees in a discussion of institutional practices that have been implemented in support of overcoming challenges, as well as provide feedback on institutional and student outcomes. The focus of this session will be on effective practice, and will be of particular interest to university administrators, educational developers, and educators wishing to implement similar initiatives on their campuses; possible adaptations for practice will be addressed. A presentation of findings from this research will be followed by an open discussion where the sharing of research, initiatives, and best practices for the enhancement of teaching and learning is welcomed. There is much insight and understanding to be gained through the sharing of ideas and collaborative practice as we move forward to further develop the program and prepare other initiatives in support of diversity and inclusion.

Keywords: eco-scale, green analysis, environmentally-friendly, pharmaceuticals analysis

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13 DH-Students Promoting Underage Asylum Seekers' Oral Health in Finland

Authors: Eeva Wallenius-Nareneva, Tuula Toivanen-Labiad

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Background: Oral health promotion event was organised for forty Afghanistan, Iraqi and Bangladeshi underage asylum seekers in Finland. The invitation to arrange this coaching occasion was accepted in the Degree Programme in Oral Hygiene in Metropolia. The personnel in the reception center found the need to improve oral health among the youngsters. The purpose was to strengthen the health literacy of the boys in their oral self-care and to reduce dental fears. The Finnish studies, especially the terminology of oral health was integrated to coaching with the help of interpreters. Cooperative learning was applied. Methods: Oral health was interactively discussed in four study group sessions: 1. The importance of healthy eating habits; - Good and bad diets, - Regular meals, - Acid attack o Xylitol. 2. Oral diseases − connection to general health; - Aetiology of gingivitis, periodontitis and caries, - Harmfulness of smoking 3. Tools and techniques for oral self-care; - Brushing and inter dental cleaning. 4. Sharing earlier dental care experiences; - Cultural differences, - Dental fear, - Regular check-ups. Results: During coaching deficiencies appeared in brushing and inter dental cleaning techniques. Some boys were used to wash their mouth with salt justifying it by salt’s antiseptic properties. Many brushed their teeth by vertical movements. The boys took feedback positively when a demonstration with model jaws revealed the inefficiency of the technique. The advantages of fluoride tooth paste were advised. Dental care procedures were new and frightening for many boys. Finnish dental care system was clarified. The safety and indolence of the treatments and informed consent were highlighted. Video presentations and the dialog lowered substantially the threshold to visit dental clinic. The occasion gave the students means for meeting patients from different cultural and language backgrounds. The information hidden behind the oral health problems of the asylum seekers was valuable. Conclusions: Learning dental care practices used in different cultures is essential for dental professionals. The project was a good start towards multicultural oral health care. More experiences are needed before graduation. Health education themes should be held simple regardless of the target group. The heterogeneity of the group does not pose a problem. Open discussion with questions leading to the theme works well in clarifying the target group’s knowledge level. Sharing own experiences strengthens the sense of equality among the participants and encourages them to express own opinions. Motivational interview method turned out to be successful. In the future coaching occasions must confirm active participation of everyone. This could be realized by dividing the participants to even smaller groups. The different languages impose challenges but they can be solved by using more interpreters. Their presence ensures that everyone understands the issues properly although the use of plain and sign languages are helpful. In further development, it would be crucial to arrange a rehearsal occasion to the same participants in two/three months’ time. This would strengthen the adaption of self-care practices and give the youngsters opportunity to pose more open questions. The students would gain valuable feedback regarding the effectiveness of their work.

Keywords: cooperative learning, interactive methods, motivational interviewing, oral health promotion, underage asylum seekers

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

Authors: Divya Palaniappan

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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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11 Gene Expression Meta-Analysis of Potential Shared and Unique Pathways Between Autoimmune Diseases Under anti-TNFα Therapy

Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

Abstract:

The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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10 Poly(Trimethylene Carbonate)/Poly(ε-Caprolactone) Phase-Separated Triblock Copolymers with Advanced Properties

Authors: Nikola Toshikj, Michel Ramonda, Sylvain Catrouillet, Jean-Jacques Robin, Sebastien Blanquer

Abstract:

Biodegradable and biocompatible block copolymers have risen as the golden materials in both medical and environmental applications. Moreover, if their architecture is of controlled manner, higher applications can be foreseen. In the meantime, organocatalytic ROP has been promoted as more rapid and immaculate route, compared to the traditional organometallic catalysis, towards efficient synthesis of block copolymer architectures. Therefore, herein we report novel organocatalytic pathway with guanidine molecules (TBD) for supported synthesis of trimethylene carbonate initiated by poly(caprolactone) as pre-polymer. Pristine PTMC-b-PCL-b-PTMC block copolymer structure, without any residual products and clear desired block proportions, was achieved under 1.5 hours at room temperature and verified by NMR spectroscopies and size-exclusion chromatography. Besides, when elaborating block copolymer films, further stability and amelioration of mechanical properties can be achieved via additional reticulation step of precedently methacrylated block copolymers. Subsequently, stimulated by the insufficient studies on the phase-separation/crystallinity relationship in these semi-crystalline block copolymer systems, their intrinsic thermal and morphology properties were investigated by differential scanning calorimetry and atomic force microscopy. Firstly, by DSC measurements, the block copolymers with χABN values superior to 20 presented two distinct glass transition temperatures, close to the ones of the respecting homopolymers, demonstrating an initial indication of a phase-separated system. In the interim, the existence of the crystalline phase was supported by the presence of melting temperature. As expected, the crystallinity driven phase-separated morphology predominated in the AFM analysis of the block copolymers. Neither crosslinking at melted state, hence creation of a dense polymer network, disturbed the crystallinity phenomena. However, the later revealed as sensible to rapid liquid nitrogen quenching directly from the melted state. Therefore, AFM analysis of liquid nitrogen quenched and crosslinked block copolymer films demonstrated a thermodynamically driven phase-separation clearly predominating over the originally crystalline one. These AFM films remained stable with their morphology unchanged even after 4 months at room temperature. However, as demonstrated by DSC analysis once rising the temperature above the melting temperature of the PCL block, neither the crosslinking nor the liquid nitrogen quenching shattered the semi-crystalline network, while the access to thermodynamical phase-separated structures was possible for temperatures under the poly (caprolactone) melting point. Precisely this coexistence of dual crosslinked/crystalline networks in the same copolymer structure allowed us to establish, for the first time, the shape-memory properties in such materials, as verified by thermomechanical analysis. Moreover, the response temperature to the material original shape depended on the block copolymer emplacement, hence PTMC or PCL as end-block. Therefore, it has been possible to reach a block copolymer with transition temperature around 40°C thus opening potential real-life medical applications. In conclusion, the initial study of phase-separation/crystallinity relationship in PTMC-b-PCL-b-PTMC block copolymers lead to the discovery of novel shape memory materials with superior properties, widely demanded in modern-life applications.

Keywords: biodegradable block copolymers, organocatalytic ROP, self-assembly, shape-memory

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9 Recent Findings of Late Bronze Age Mining and Archaeometallurgy Activities in the Mountain Region of Colchis (Southern Lechkhumi, Georgia)

Authors: Rusudan Chagelishvili, Nino Sulava, Tamar Beridze, Nana Rezesidze, Nikoloz Tatuashvili

Abstract:

The South Caucasus is one of the most important centers of prehistoric metallurgy, known for its Colchian bronze culture. Modern Lechkhumi – historical Mountainous Colchis where the existence of prehistoric metallurgy is confirmed by the discovery of many artifacts is a part of this area. Studies focused on prehistoric smelting sites, related artefacts, and ore deposits have been conducted during last ten years in Lechkhumi. More than 20 prehistoric smelting sites and artefacts associated with metallurgical activities (ore roasting furnaces, slags, crucible, and tuyères fragments) have been identified so far. Within the framework of integrated studies was established that these sites were operating in 13-9 centuries B.C. and used for copper smelting. Palynological studies of slags revealed that chestnut (Castanea sativa) and hornbeam (Carpinus sp.) wood were used as smelting fuel. Geological exploration-analytical studies revealed that copper ore mining, processing, and smelting sites were distributed close to each other. Despite recent complex data, the signs of prehistoric mines (trenches) haven’t been found in this part of the study area so far. Since 2018 the archaeological-geological exploration has been focused on the southern part of Lechkhumi and covered the areas of villages Okureshi and Opitara. Several copper smelting sites (Okureshi 1 and 2, Opitara 1), as well as a Colchian Bronze culture settlement, have been identified here. Three mine workings have been found in the narrow gorge of the river Rtkhmelebisgele in the vicinities of the village Opitara. In order to establish a link between the Opitara-Okureshi archaeometallurgical sites, Late Bronze Age settlements, and mines, various scientific analytical methods -mineralized rock and slags petrography and atomic absorption spectrophotometry (AAS) analysis have been applied. The careful examination of Opitara mine workings revealed that there is a striking difference between the mine #1 on the right bank of the river and mines #2 and #3 on the left bank. The first one has all characteristic features of the Soviet period mine working (e. g. high portal with angular ribs and roof showing signs of blasting). In contrast, mines #2 and #3, which are located very close to each other, have round-shaped portals/entrances, low roofs, and fairly smooth ribs and are filled with thick layers of river sediments and collapsed weathered rock mass. A thorough review of the publications related to prehistoric mine workings revealed some striking similarities between mines #2 and #3 with their worldwide analogues. Apparently, the ore extraction from these mines was conducted by fire-setting applying primitive tools. It was also established that mines are cut in Jurassic mineralized volcanic rocks. Ore minerals (chalcopyrite, pyrite, galena) are related to calcite and quartz veins. The results obtained through the petrochemical and petrography studies of mineralized rock samples from Opitara mines and prehistoric slags are in complete correlation with each other, establishing the direct link between copper mining and smelting within the study area. Acknowledgment: This work was supported by the Shota Rustaveli National Science Foundation of Georgia (grant # FR-19-13022).

Keywords: archaeometallurgy, Mountainous Colchis, mining, ore minerals

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8 Investigation of the Controversial Immunomodulatory Potential of Trichinella spiralis Excretory-Secretory Products versus Extracellular Vesicles Derived from These Products in vitro

Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

Abstract:

As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

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7 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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6 Study of Objectivity, Reliability and Validity of Pedagogical Diagnostic Parameters Introduced in the Framework of a Specific Research

Authors: Emiliya Tsankova, Genoveva Zlateva, Violeta Kostadinova

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The challenges modern education faces undoubtedly require reforms and innovations aimed at the reconceptualization of existing educational strategies, the introduction of new concepts and novel techniques and technologies related to the recasting of the aims of education and the remodeling of the content and methodology of education which would guarantee the streamlining of our education with basic European values. Aim: The aim of the current research is the development of a didactic technology for the assessment of the applicability and efficacy of game techniques in pedagogic practice calibrated to specific content and the age specificity of learners, as well as for evaluating the efficacy of such approaches for the facilitation of the acquisition of biological knowledge at a higher theoretical level. Results: In this research, we examine the objectivity, reliability and validity of two newly introduced diagnostic parameters for assessing the durability of the acquired knowledge. A pedagogic experiment has been carried out targeting the verification of the hypothesis that the introduction of game techniques in biological education leads to an increase in the quantity, quality and durability of the knowledge acquired by students. For the purposes of monitoring the effect of the application of the pedagogical technique employing game methodology on the durability of the acquired knowledge a test-base examination has been applied to students from a control group (CG) and students form an experimental group on the same content after a six-month period. The analysis is based on: 1.A study of the statistical significance of the differences of the tests for the CG and the EG, applied after a six-month period, which however is not indicative of the presence or absence of a marked effect from the applied pedagogic technique in cases when the entry levels of the two groups are different. 2.For a more reliable comparison, independently from the entry level of each group, another “indicator of efficacy of game techniques for the durability of knowledge” which has been used for the assessment of the achievement results and durability of this methodology of education. The monitoring of the studied parameters in their dynamic unfolding in different age groups of learners unquestionably reveals a positive effect of the introduction of game techniques in education in respect of durability and permanence of acquired knowledge. Methods: In the current research the following battery of methods and techniques of research for diagnostics has been employed: theoretical analysis and synthesis; an actual pedagogical experiment; questionnaire; didactic testing and mathematical and statistical methods. The data obtained have been used for the qualitative and quantitative of the results which reflect the efficacy of the applied methodology. Conclusion: The didactic model of the parameters researched in the framework of a specific study of pedagogic diagnostics is based on a general, interdisciplinary approach. Enhanced durability of the acquired knowledge proves the transition of that knowledge from short-term memory storage into long-term memory of pupils and students, which justifies the conclusion that didactic plays have beneficial effects for the betterment of learners’ cognitive skills. The innovations in teaching enhance the motivation, creativity and independent cognitive activity in the process of acquiring the material thought. The innovative methods allow for untraditional means for assessing the level of knowledge acquisition. This makes possible the timely discovery of knowledge gaps and the introduction of compensatory techniques, which in turn leads to deeper and more durable acquisition of knowledge.

Keywords: objectivity, reliability and validity of pedagogical diagnostic parameters introduced in the framework of a specific research

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5 Pharmacophore-Based Modeling of a Series of Human Glutaminyl Cyclase Inhibitors to Identify Lead Molecules by Virtual Screening, Molecular Docking and Molecular Dynamics Simulation Study

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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