Search results for: targeting logic
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1264

Search results for: targeting logic

64 The 5-HT1A Receptor Biased Agonists, NLX-101 and NLX-204, Elicit Rapid-Acting Antidepressant Activity in Rat Similar to Ketamine and via GABAergic Mechanisms

Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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63 The Location of Park and Ride Facilities Using the Fuzzy Inference Model

Authors: Anna Lower, Michal Lower, Robert Masztalski, Agnieszka Szumilas

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Contemporary cities are facing serious congestion and parking problems. In urban transport policy the introduction of the park and ride system (P&R) is an increasingly popular way of limiting vehicular traffic. The determining of P&R facilities location is a key aspect of the system. Criteria for assessing the quality of the selected location are formulated generally and descriptively. The research outsourced to specialists are expensive and time consuming. The most focus is on the examination of a few selected places. The practice has shown that the choice of the location of these sites in a intuitive way without a detailed analysis of all the circumstances, often gives negative results. Then the existing facilities are not used as expected. Methods of location as a research topic are also widely taken in the scientific literature. Built mathematical models often do not bring the problem comprehensively, e.g. assuming that the city is linear, developed along one important communications corridor. The paper presents a new method where the expert knowledge is applied to fuzzy inference model. With such a built system even a less experienced person could benefit from it, e.g. urban planners, officials. The analysis result is obtained in a very short time, so a large number of the proposed location can also be verified in a short time. The proposed method is intended for testing of car parks location in a city. The paper will show selected examples of locations of the P&R facilities in cities planning to introduce the P&R. The analysis of existing objects will also be shown in the paper and they will be confronted with the opinions of the system users, with particular emphasis on unpopular locations. The research are executed using the fuzzy inference model which was built and described in more detail in the earlier paper of the authors. The results of analyzes are compared to documents of P&R facilities location outsourced by the city and opinions of existing facilities users expressed on social networking sites. The research of existing facilities were conducted by means of the fuzzy model. The results are consistent with actual users feedback. The proposed method proves to be good, but does not require the involvement of a large experts team and large financial contributions for complicated research. The method also provides an opportunity to show the alternative location of P&R facilities. The performed studies show that the method has been confirmed. The method can be applied in urban planning of the P&R facilities location in relation to the accompanying functions. Although the results of the method are approximate, they are not worse than results of analysis of employed experts. The advantage of this method is ease of use, which simplifies the professional expert analysis. The ability of analyzing a large number of alternative locations gives a broader view on the problem. It is valuable that the arduous analysis of the team of people can be replaced by the model's calculation. According to the authors, the proposed method is also suitable for implementation on a GIS platform.

Keywords: fuzzy logic inference, park and ride system, P&R facilities, P&R location

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62 Engineering Photodynamic with Radioactive Therapeutic Systems for Sustainable Molecular Polarity: Autopoiesis Systems

Authors: Moustafa Osman Mohammed

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This paper introduces Luhmann’s autopoietic social systems starting with the original concept of autopoiesis by biologists and scientists, including the modification of general systems based on socialized medicine. A specific type of autopoietic system is explained in the three existing groups of the ecological phenomena: interaction, social and medical sciences. This hypothesis model, nevertheless, has a nonlinear interaction with its natural environment ‘interactional cycle’ for the exchange of photon energy with molecular without any changes in topology. The external forces in the systems environment might be concomitant with the natural fluctuations’ influence (e.g. radioactive radiation, electromagnetic waves). The cantilever sensor deploys insights to the future chip processor for prevention of social metabolic systems. Thus, the circuits with resonant electric and optical properties are prototyped on board as an intra–chip inter–chip transmission for producing electromagnetic energy approximately ranges from 1.7 mA at 3.3 V to service the detection in locomotion with the least significant power losses. Nowadays, therapeutic systems are assimilated materials from embryonic stem cells to aggregate multiple functions of the vessels nature de-cellular structure for replenishment. While, the interior actuators deploy base-pair complementarity of nucleotides for the symmetric arrangement in particular bacterial nanonetworks of the sequence cycle creating double-stranded DNA strings. The DNA strands must be sequenced, assembled, and decoded in order to reconstruct the original source reliably. The design of exterior actuators have the ability in sensing different variations in the corresponding patterns regarding beat-to-beat heart rate variability (HRV) for spatial autocorrelation of molecular communication, which consists of human electromagnetic, piezoelectric, electrostatic and electrothermal energy to monitor and transfer the dynamic changes of all the cantilevers simultaneously in real-time workspace with high precision. A prototype-enabled dynamic energy sensor has been investigated in the laboratory for inclusion of nanoscale devices in the architecture with a fuzzy logic control for detection of thermal and electrostatic changes with optoelectronic devices to interpret uncertainty associated with signal interference. Ultimately, the controversial aspect of molecular frictional properties is adjusted to each other and forms its unique spatial structure modules for providing the environment mutual contribution in the investigation of mass temperature changes due to pathogenic archival architecture of clusters.

Keywords: autopoiesis, nanoparticles, quantum photonics, portable energy, photonic structure, photodynamic therapeutic system

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61 Isolation of Bacterial Species with Potential Capacity for Siloxane Removal in Biogas Upgrading

Authors: Ellana Boada, Eric Santos-Clotas, Alba Cabrera-Codony, Maria Martin, Lluis Baneras, Frederic Gich

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Volatile methylsiloxanes (VMS) are a group of manmade silicone compounds widely used in household and industrial applications that end up on the biogas produced through the anaerobic digestion of organic matter in landfills and wastewater treatment plants. The presence of VMS during the biogas energy conversion can cause damage on the engines, reducing the efficiency of this renewable energy source. Non regenerative adsorption onto activated carbon is the most widely used technology to remove siloxanes from biogas, while new trends point out that biotechnology offers a low-cost and environmentally friendly alternative to conventional technologies. The first objective of this research was to enrich, isolate and identify bacterial species able to grow using siloxane molecules as a sole carbon source: anoxic wastewater sludge was used as initial inoculum in liquid anoxic enrichments, adding D4 (as representative siloxane compound) previously adsorbed on activated carbon. After several months of acclimatization, liquid enrichments were plated onto solid media containing D4 and thirty-four bacterial isolates were obtained. 16S rRNA gene sequencing allowed the identification of strains belonging to the following species: Ciceribacter lividus, Alicycliphilus denitrificans, Pseudomonas aeruginosa and Pseudomonas citronellolis which are described to be capable to degrade toxic volatile organic compounds. Kinetic assays with 8 representative strains revealed higher cell growth in the presence of D4 compared to the control. Our second objective was to characterize the community composition and diversity of the microbial community present in the enrichments and to elucidate whether the isolated strains were representative members of the community or not. DNA samples were extracted, the 16S rRNA gene was amplified (515F & 806R primer pair), and the microbiome analyzed from sequences obtained with a MiSeq PE250 platform. Results showed that the retrieved isolates only represented a minor fraction of the microorganisms present in the enrichment samples, which were represented by Alpha, Beta, and Gamma proteobacteria as dominant groups in the category class thus suggesting that other microbial species and/or consortia may be important for D4 biodegradation. These results highlight the need of additional protocols for the isolation of relevant D4 degraders. Currently, we are developing molecular tools targeting key genes involved in siloxane biodegradation to identify and quantify the capacity of the isolates to metabolize D4 in batch cultures supplied with a synthetic gas stream of air containing 60 mg m⁻³ of D4 together with other volatile organic compounds found in the biogas mixture (i.e. toluene, hexane and limonene). The isolates were used as inoculum in a biotrickling filter containing lava rocks and activated carbon to assess their capacity for siloxane removal. Preliminary results of biotrickling filter performance showed 35% of siloxane biodegradation in a contact time of 14 minutes, denoting that biological siloxane removal is a promising technology for biogas upgrading.

Keywords: bacterial cultivation, biogas upgrading, microbiome, siloxanes

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60 From the Classroom to Digital Learning Environments: An Action Research on Pedagogical Practices in Higher Education

Authors: Marie Alexandre, Jean Bernatchez

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This paper focuses on the complexity of the face-to-face-to-distance learning transition process. Our research action aims to support the process of transition from classroom to distance learning for teachers in higher education with regard to pedagogical practices that can meet the various needs of students using digital learning environments. In Quebec and elsewhere in the world, the advent of digital education is helping to transform teaching, which is significantly changing the role of teachers. While distance education implies a dissociation of teaching and learning to a variable degree in space and time, distance education (DE) is becoming more and increasingly becoming a preferred option for maintaining the delivery of certain programs and providing access to programs and to provide access to quality activities throughout Quebec. Given the impact of teaching practices on educational success, this paper reports on the results of three research objectives: 1) To document teachers' knowledge of teaching in distance education through the design, experimentation and production of a repertoire of the determinants of pedagogical practices in response to students' needs. 2) Explain, according to a gendered logic, the adequacy between the pedagogical practices implemented in distance learning and the response to the profiles and needs expressed by students using digital learning environments; 3) Produce a model of a support approach during the process of transition from classroom to distance learning at the college level. A mixed methodology, i.e., a quantitative component (questionnaire survey) and a qualitative component (explanatory interviews and living lab) was used in cycles that were part of an ongoing validation process. The intervention includes the establishment of a professional collaboration group, webinars training webinars for the participating teachers on the didactic issue of knowledge-teaching in FAD, the didactic use of technologies, and the differentiated socialization models of educational success in college education. All of the tools developed will be used by partners in the target environment as well as by all teacher educators, students in initial teacher training, practicing teachers, and the general public. The results show that access to training leading to qualifications and commitment to educational success reflects the existing links between the people in the educational community. The relational stakes of being present in distance education take on multiple configurations and different dimensions of learning testify to needs and realities that are sometimes distinct depending on the life cycle. This project will be of interest to partners in the targeted field as well as to all teacher trainers, students in initial teacher training, practicing college teachers, and to university professors. The entire educational community will benefit from digital resources in education. The scientific knowledge resulting from this action research will benefit researchers in the fields of pedagogy, didactics, teacher training and pedagogy in higher education in a digital context.

Keywords: action research, didactics, digital learning environment, distance learning, higher education, pedagogy technological, pedagogical content knowledge

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59 Differential Expression Profile Analysis of DNA Repair Genes in Mycobacterium Leprae by qPCR

Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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58 A Socio-Spatial Analysis of Financialization and the Formation of Oligopolies in Brazilian Basic Education

Authors: Gleyce Assis Da Silva Barbosa

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In recent years, we have witnessed a vertiginous growth of large education companies. Daughters of national and world capital, these companies expand both through consolidated physical networks in the form of branches spread across the territory and through institutional networks such as business networks through mergers, acquisitions, creation of new companies and influence. They do this by incorporating small, medium and large schools and universities, teaching systems and other products and services. They are also able to weave their webs directly or indirectly in philanthropic circles, limited partnerships, family businesses and even in public education through various mechanisms of outsourcing, privatization and commercialization of products for the sector. Although the growth of these groups in basic education seems to us a recent phenomenon in peripheral countries such as Brazil, its diffusion is closely linked to higher education conglomerates and other sectors of the economy forming oligopolies, which began to expand in the 1990s with strong state support and through political reforms that redefined its role, transforming it into a fundamental agent in the formation of guidelines to boost the incorporation of neoliberal logic. This expansion occurred through the objectification of education, commodifying it and transforming students into consumer clients. Financial power combined with the neo-liberalization of state public policies allowed the profusion of social exclusion, the increase of individuals without access to basic services, deindustrialization, automation, capital volatility and the indetermination of the economy; in addition, this process causes capital to be valued and devalued at rates never seen before, which together generates various impacts such as the precariousness of work. Understanding the connection between these processes, which engender the economy, allows us to see their consequences in labor relations and in the territory. In this sense, it is necessary to analyze the geographic-economic context and the role of the facilitating agents of this process, which can give us clues about the ongoing transformations and the directions of education in the national and even international scenario since this process is linked to the multiple scales of financial globalization. Therefore, the present research has the general objective of analyzing the socio-spatial impacts of financialization and the formation of oligopolies in Brazilian basic education. For this, the survey of laws, data, and public policies on the subject in question was used as a methodology. As a methodology, the work was based on some data from these companies available on websites for investors. Survey of information from global and national companies that operate in Brazilian basic education. In addition to mapping the expansion of educational oligopolies using public data on the location of schools. With this, the research intends to provide information about the ongoing commodification process in the country. Discuss the consequences of the oligopolization of education, considering the impacts that financialization can bring to teaching work.

Keywords: financialization, oligopolies, education, Brazil

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57 The Messy and Irregular Experience of Entrepreneurial Life

Authors: Hannah Dean

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The growth ideology, and its association with progress, is an important construct in the narrative of modernity. This ideology is embedded in neoclassical economic growth theory which conceptualises growth as linear and predictable, and the entrepreneur as a rational economic manager. This conceptualisation has been critiqued for reinforcing the managerial discourse in entrepreneurship studies. Despite these critiques, both the neoclassical growth theory and its adjacent managerial discourse dominate entrepreneurship studies notably the literature on female entrepreneurs. The latter is the focus of this paper. Given this emphasis on growth, female entrepreneurs are portrayed as problematic because their growth lags behind their male counterparts. This image which ignores the complexity and diversity of female entrepreneurs’ experience persists in the literature due to the lack of studies that analyse the process and contextual factors surrounding female entrepreneurs’ experience. This study aims to address the subordination of female entrepreneurs by questioning the hegemonic logic of economic growth and the managerial discourse as a true representation for the entrepreneurial experience. This objective is achieved by drawing on Schumpeter’s theorising and narrative inquiry. This exploratory study undertakes in depth interviews to gain insights into female entrepreneurs’ experience and the impact of the economic growth model and the managerial discourse on their performance. The narratives challenge a number of assumptions about female entrepreneurs. The participants occupied senior positions in the corporate world before setting up their businesses. This is at odds with much writing which assumes that women underperform because they leave their career without gaining managerial experience to achieve work-life balance. In line with Schumpeter, who distinguishes the entrepreneur from the manager, the participants’ main function was innovation. They did not believe that the managerial paradigm governing their corporate careers was applicable to their entrepreneurial experience. Formal planning and managerial rationality can hinder their decision making process. The narratives point to the gap between the two worlds which makes stepping into entrepreneurship a scary move. Schumpeter argues that the entrepreneurial process is evolutionary and that failure is an integral part of it. The participants’ entrepreneurial process was in fact irregular. The performance of new combinations was not always predictable. They therefore relied on their initiative. The inhibition to deploy these traits had an adverse effect on business growth. The narratives also indicate that over-reliance on growth threaten the business survival as it faces competing pressures. The study offers theoretical and empirical contributions to (female) entrepreneurship studies by presenting Schumpeter’s theorising as an alternative theoretical framework to the neoclassical economic growth theory. The study also reduces entrepreneurs’ vulnerability by making them aware of the negative influence that the linear growth model and the managerial discourse hold upon their performance. The study has implications for policy makers as it generates new knowledge that incorporates the current social and economic changes in the context of entrepreneurs that can no longer be sustained by the linear growth models especially in the current economic climate.

Keywords: economic growth, female entrepreneurs, managerial discourse, Schumpeter

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56 Impact of Transgenic Adipose Derived Stem Cells in the Healing of Spinal Cord Injury of Dogs

Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon

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The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs

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55 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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54 Redox-labeled Electrochemical Aptasensor Array for Single-cell Detection

Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément

Abstract:

The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

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53 Mental Health Promotion for Children of Mentally Ill Parents in Schools. Assessment and Promotion of Teacher Mental Health Literacy in Order to Promote Child Related Mental Health (Teacher-MHL)

Authors: Dirk Bruland, Paulo Pinheiro, Ullrich Bauer

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Introduction: Over 3 million children, about one quarter of all students, experience at least one parent with mental disorder in Germany every year. Children of mentally-ill parents are at considerably higher risk of developing serious mental health problems. The different burden patterns and coping attempts often become manifest in children's school lives. In this context, schools can have an important protective function, but can also create risk potentials. In reference to Jorm, pupil-related teachers’ mental health literacy (Teacher-MHL) includes the ability to recognize change behaviour, the knowledge of risk factors, the implementation of first aid intervention, and seeking professional help (teacher as gatekeeper). Although teachers’ knowledge and increased awareness of this topic is essential, the literature provides little information on the extent of teachers' abilities. As part of a German-wide research consortium on health literacy, this project, launched in March for 3 years, will conduct evidence-based mental health literacy research. The primary objective is to measure Teacher-MHL in the context of pupil-related psychosocial factors at primary and secondary schools (grades 5 & 6), while also focussing on children’s social living conditions. Methods: (1) A systematic literature review in different databases to identify papers with regard to Teacher-MHL (completed). (2) Based on these results, an interview guide was developed. This research step includes a qualitative pre-study to inductively survey the general profiles of teachers (n=24). The evaluation will be presented on the conference. (3) These findings will be translated into a quantitative teacher survey (n=2500) in order to assess the extent of socio-analytical skills of teachers as well as in relation to institutional and individual characteristics. (4) Based on results 1 – 3, developing a training program for teachers. Results: The review highlights a lack of information for Teacher-MHL and their skills, especially related to high-risk-groups like children of mentally ill parents. The literature is limited to a few studies only. According to these, teacher are not good at identifying burdened children and if they identify those children they do not know how to handle the situations in school. They are not sufficiently trained to deal with these children, especially there are great uncertainties in dealing with the teaching situation. Institutional means and resources are missing as well. Such a mismatch can result in insufficient support and use of opportunities for children at risk. First impressions from the interviews confirm these results and allow a greater insight in the everyday school-life according to critical life events in families. Conclusions: For the first time schools will be addressed as a setting where children are especially "accessible" for measures of health promotion. Addressing Teacher-MHL gives reason to expect high effectiveness. Targeting professionals' abilities for dealing with this high-risk-group leads to a discharge for teacher themselves to handle those situations and increases school health promotion. In view of the fact that only 10-30% of such high-risk families accept offers of therapy and assistance, this will be the first primary preventive and health-promoting approach to protect the health of a yet unaffected, but particularly burdened, high-risk group.

Keywords: children of mentally ill parents, health promotion, mental health literacy, school

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52 Biosynthesis of a Nanoparticle-Antibody Phthalocyanine Photosensitizer for Use in Targeted Photodynamic Therapy of Cervical Cancer

Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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51 The Connection between Qom Seminaries and Interpretation of Sacred Sources in Ja‘farī Jurisprudence

Authors: Sumeyra Yakar, Emine Enise Yakar

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Iran presents itself as Islamic, first and foremost, and thus, it can be said that sharī’a is the political and social centre of the states. However, actual practice reveals distinct interpretations and understandings of the sharī’a. The research can be categorised inside the framework of logic in Islamic law and theology. The first task of this paper will be to identify how the sharī’a is understood in Iran by mapping out how the judges apply the law in their respective jurisdictions. The attention will then move from a simple description of the diversity of sharī’a understandings to the question of how that diversity relates to social concepts and cultures. This, of course, necessitates a brief exploration of Iran’s historical background which will also allow for an understanding of sectarian influences and the significance of certain events. The main purpose is to reach an understanding of the process of applying sources to formulate solutions which are in accordance with sharī’a and how religious education is pursued in order to become official judges. Ultimately, this essay will explore the attempts to gain an understanding by linking the practices to the secondary sources of Islamic law. It is important to emphasise that these cultural components of Islamic law must be compatible with the aims of Islamic law and their fundamental sources. The sharī’a consists of more than just legal doctrines (fiqh) and interpretive activities (ijtihād). Its contextual and theoretical framework reveals a close relationship with cultural and historical elements of society. This has meant that its traditional reproduction over time has relied on being embedded into a highly particular form of life. Thus, as acknowledged by pre-modern jurists, the sharī’a encompasses a comprehensive approach to the requirements of justice in legal, historical and political contexts. In theological and legal areas that have the specific authority of tradition, Iran adheres to Shīa’ doctrine, and this explains why the Shīa’ religious establishment maintains a dominant position in matters relating to law and the interpretation of sharī’a. The statements and interpretations of the tradition are distinctly different from sunnī interpretations, and so the use of different sources could be understood as the main reason for the discrepancies in the application of sharī’a between Iran and other Muslim countries. The sharī’a has often accommodated prevailing customs; moreover, it has developed legal mechanisms to all for its adaptation to particular needs and circumstances in society. While jurists may operate within the realm of governance and politics, the moral authority of the sharī’a ensures that these actors legitimate their actions with reference to God’s commands. The Iranian regime enshrines the principle of vilāyāt-i faqīh (guardianship of the jurist) which enables jurists to solve the conflict between law as an ideal system, in theory, and law in practice. The paper aims to show how the religious, educational system works in harmony with the governmental authorities with the concept of vilāyāt-i faqīh in Iran and contributes to the creation of religious custom in the society.

Keywords: guardianship of the jurist (vilāyāt-i faqīh), imitation (taqlīd), seminaries (hawza), Shi’i jurisprudence

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50 Presenting Research-Based Mindfulness Tools for Corporate Wellness

Authors: Dana Zelicha

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The objective of this paper is to present innovative mindfulness tools specifically designed by OWBA—The Well Being Agency for organisations and corporate wellness programmes. The OWBA Mindfulness Tools (OWBA-MT) consist of practical mindfulness exercises to educate and train employees and business leaders to think, feel, and act more mindfully. Among these cutting-edge interventions are Mindful Meetings, Mindful Decision Making and Unitasking activities, intended to cultivate mindful communication and compassion in the workplace and transform organisational culture. In addition to targeting CEO’s and leaders within large corporations, OWBA-MT is also directed at the needs of specific populations such as entrepreneurs’ resilience and women empowerment. The goals of the OWBA-MT are threefold: to inform, inspire and implement. The first goal is to inform participants about the relationship between workplace stress, distractibility and miscommunication in the framework of mindfulness. The second goal is for the audience to be inspired to share those practices with other members of their organisation. The final objective is to equip participants with the tools to foster a compassionate, mindful and well-balanced work environment. To assess these tools, a 6-week case study was conducted as part of an employee wellness programme for a large international corporation. The OWBA-MT were introduced in a workshop forum once-a-week, with participants practicing these tools both in the office and at home. The workshops occurred 1 day a week (2 hours each), with themes and exercises varying weekly. To reinforce practice at home, participants received reflection forms and guided meditations online. Materials were sent via-email at the same time each day to ensure consistency and participation. To evaluate the effectiveness of the mindfulness intervention, improvements in four categories were measured: listening skills, mindfulness levels, prioritising skills and happiness levels. These factors were assessed using online self-reported questionnaires administered at the start of the intervention, and then again 4-weeks following completion. The measures included the Mindfulness Attention Awareness Scale (MAAS), Listening Skills Inventory (LSI), Time Management Behaviour Scale (TMBS) and a modified version of the Oxford Happiness Questionnaire (OHQ). All four parameters showed significant improvements from the start of the programme to the 4-week follow-up. Participant testimonials exhibited high levels of satisfaction and the overall results indicate that the OWBA-MT intervention substantially impacted the corporation in a positive way. The implications of these results suggest that OWBA-MT can improve employees’ capacities to listen and work well with others, to manage time effectively, and to experience enhanced satisfaction both at work and in life. Although corporate mindfulness programmes have proven to be effective, the challenge remains the low engagement levels at home in between training sessions and to implement the tools beyond the scope of the intervention. OWBA-MT has offered an innovative approach to enforce engagement levels at home by sending daily online materials outside the workshop forum with a personalised response. The limitations also noteworthy to consider for future research include the afterglow effect and lack of generalisability, as this study was conducted on a small and fairly homogenous sample.

Keywords: corporate mindfulness, listening skills, mindful leadership, mindfulness tools, organisational well being

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49 Scenarios of Digitalization and Energy Efficiency in the Building Sector in Brazil: 2050 Horizon

Authors: Maria Fatima Almeida, Rodrigo Calili, George Soares, João Krause, Myrthes Marcele Dos Santos, Anna Carolina Suzano E. Silva, Marcos Alexandre Da

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In Brazil, the building sector accounts for 1/6 of energy consumption and 50% of electricity consumption. A complex sector with several driving actors plays an essential role in the country's economy. Currently, the digitalization readiness in this sector is still low, mainly due to the high investment costs and the difficulty of estimating the benefits of digital technologies in buildings. Nevertheless, the potential contribution of digitalization for increasing energy efficiency in the building sector in Brazil has been pointed out as relevant in the political and sectoral contexts, both in the medium and long-term horizons. To contribute to the debate on the possible evolving trajectories of digitalization in the building sector in Brazil and to subsidize the formulation or revision of current public policies and managerial decisions, three future scenarios were created to anticipate the potential energy efficiency in the building sector in Brazil due to digitalization by 2050. This work aims to present these scenarios as a basis to foresight the potential energy efficiency in this sector, according to different digitalization paces - slow, moderate, or fast in the 2050 horizon. A methodological approach was proposed to create alternative prospective scenarios, combining the Global Business Network (GBN) and the Laboratory for Investigation in Prospective Strategy and Organisation (LIPSOR) methods. This approach consists of seven steps: (i) definition of the question to be foresighted and time horizon to be considered (2050); (ii) definition and classification of a set of key variables, using the prospective structural analysis; (iii) identification of the main actors with an active role in the digital and energy spheres; (iv) characterization of the current situation (2021) and identification of main uncertainties that were considered critical in the development of alternative future scenarios; (v) scanning possible futures using morphological analysis; (vi) selection and description of the most likely scenarios; (vii) foresighting the potential energy efficiency in each of the three scenarios, namely slow digitalization; moderate digitalization, and fast digitalization. Each scenario begins with a core logic and then encompasses potentially related elements, including potential energy efficiency. Then, the first scenario refers to digitalization at a slow pace, with induction by the government limited to public buildings. In the second scenario, digitalization is implemented at a moderate pace, induced by the government in public, commercial, and service buildings, through regulation integrating digitalization and energy efficiency mechanisms. Finally, in the third scenario, digitalization in the building sector is implemented at a fast pace in the country and is strongly induced by the government, but with broad participation of private investments and accelerated adoption of digital technologies. As a result of the slow pace of digitalization in the sector, the potential for energy efficiency stands at levels below 10% of the total of 161TWh by 2050. In the moderate digitalization scenario, the potential reaches 20 to 30% of the total 161TWh by 2050. Furthermore, in the rapid digitalization scenario, it will reach 30 to 40% of the total 161TWh by 2050.

Keywords: building digitalization, energy efficiency, scenario building, prospective structural analysis, morphological analysis

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48 A Critical Evaluation of Occupational Safety and Health Management Systems' Implementation: Case of Mutare Urban Timber Processing Factories, Zimbabwe

Authors: Johanes Mandowa

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The study evaluated the status of Occupational Safety and Health Management Systems’ (OSHMSs) implementation by Mutare urban timber processing factories. A descriptive cross sectional survey method was utilized in the study. Questionnaires, interviews and direct observations were the techniques employed to extract primary data from the respondents. Secondary data was acquired from OSH encyclopedia, OSH journals, newspaper articles, internet, past research papers, African Newsletter on OSH and NSSA On-guard magazines among others. Analysis of data collected was conducted using statistical and descriptive methods. Results revealed an unpleasant low uptake rate (16%) of OSH Management Systems by Mutare urban timber processing factories. On a comparative basis, low implementation levels were more pronounced in small timber processing factories than in large factories. The low uptake rate of OSH Management Systems revealed by the study validates the Government of Zimbabwe and its social partners’ observation that the dismal Zimbabwe OSH performance was largely due to non implementation of safety systems at most workplaces. The results exhibited a relationship between availability of a SHE practitioner in Mutare urban timber processing factories and OSHMS implementation. All respondents and interviewees’ agreed that OSH Management Systems are handy in curbing occupational injuries and diseases. It emerged from the study that the top barriers to implementation of safety systems are lack of adequate financial resources, lack of top management commitment and lack of OSHMS implementation expertise. Key motivators for OSHMSs establishment were cited as provision of adequate resources (76%), strong employee involvement (64%) and strong senior management commitment and involvement (60%). Study results demonstrated that both OSHMSs implementation barriers and motivators affect all Mutare urban timber processing factories irrespective of size. The study recommends enactment of a law by Ministry of Public Service, Labour and Social Welfare in consultation with NSSA to make availability of an OSHMS and qualified SHE practitioner mandatory at every workplace. More so, the enacted law should prescribe minimum educational qualification required for one to practice as a SHE practitioner. Ministry of Public Service, Labour and Social Welfare and NSSA should also devise incentives such as reduced WCIF premiums for good OSH performance to cushion Mutare urban timber processing factories from OSHMS implementation costs. The study recommends the incorporation of an OSH module in the academic curriculums of all programmes offered at tertiary institutions so as to ensure that graduates who later end up assuming influential management positions in Mutare urban timber processing factories are abreast with the necessity of OSHMSs in preventing occupational injuries and diseases. In the quest to further boost management’s awareness on the importance of OSHMSs, NSSA and SAZ are urged by the study to conduct OSHMSs awareness breakfast meetings targeting executive management on a periodic basis. The Government of Zimbabwe through the Ministry of Public Service, Labour and Social Welfare should also engage ILO Country Office for Zimbabwe to solicit for ILO’s technical assistance so as to enhance the effectiveness of NSSA’s and SAZ’s OSHMSs promotional programmes.

Keywords: occupational safety health management system, national social security authority, standard association of Zimbabwe, Mutare urban timber processing factories, ministry of public service, labour and social welfare

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47 Agri-Food Transparency and Traceability: A Marketing Tool to Satisfy Consumer Awareness Needs

Authors: Angelo Corallo, Maria Elena Latino, Marta Menegoli

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The link between man and food plays, in the social and economic system, a central role where cultural and multidisciplinary aspects intertwine: food is not only nutrition, but also communication, culture, politics, environment, science, ethics, fashion. This multi-dimensionality has many implications in the food economy. In recent years, the consumer became more conscious about his food choices, involving a consistent change in consumption models. This change concerns several aspects: awareness of food system issues, employment of socially and environmentally conscious decision-making, food choices based on different characteristics than nutritional ones i.e. origin of food, how it’s produced, and who’s producing it. In this frame the ‘consumption choices’ and the ‘interests of the citizen’ become one part of the others. The figure of the ‘Citizen Consumer’ is born, a responsible and ethically motivated individual to change his lifestyle, achieving the goal of sustainable consumption. Simultaneously the branding, that before was guarantee of the product quality, today is questioned. In order to meet these needs, Agri-Food companies are developing specific product lines that follow two main philosophies: ‘Back to basics’ and ‘Less is more’. However, the issue of ethical behavior does not seem to find an adequate on market offer. Most likely due to a lack of attention on the communication strategy used, very often based on market logic and rarely on ethical one. The label in its classic concept of ‘clean labeling’ can no longer be the only instrument through which to convey product information and its evolution towards a concept of ‘clear label’ is necessary to embrace ethical and transparent concepts in progress the process of democratization of the Food System. The implementation of a voluntary traceability path, relying on the technological models of the Internet of Things or Industry 4.0, would enable the Agri-Food Supply Chain to collect data that, if properly treated, could satisfy the information need of consumers. A change of approach is therefore proposed towards Agri-Food traceability that is no longer intended as a tool to be used to respond to the legislator, but rather as a promotional tool useful to tell the company in a transparent manner and then reach the slice of the market of food citizens. The use of mobile technology can also facilitate this information transfer. However, in order to guarantee maximum efficiency, an appropriate communication model based on the ethical communication principles should be used, which aims to overcome the pipeline communication model, to offer the listener a new way of telling the food product, based on real data collected through processes traceability. The Citizen Consumer is therefore placed at the center of the new model of communication in which he has the opportunity to choose what to know and how. The new label creates a virtual access point capable of telling the product according to different point of views, following the personal interests and offering the possibility to give several content modalities to support different situations and usability.

Keywords: agri food traceability, agri-food transparency, clear label, food system, internet of things

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46 Integrated Mathematical Modeling and Advance Visualization of Magnetic Nanoparticle for Drug Delivery, Drug Release and Effects to Cancer Cell Treatment

Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

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This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

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45 India’s Foreign Policy toward its South Asian Neighbors: Retrospect and Prospect

Authors: Debasish Nandy

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India’s foreign policy towards all of her neighbor countries is determinate on the basis of multi-dimensional factors. India’s relations with its South Asian neighbor can be classified into three categories. In the first category, there are four countries -Sri Lanka, Bangladesh, Nepal, and Afghanistan- whose bilateral relationships have encompassed cooperation, irritants, problems and crisis at different points in time. With Pakistan, the relationship has been perpetually adversarial. The third category includes Bhutan and Maldives whose relations are marked by friendship and cooperation, free of any bilateral problems. It is needless to say that Jawaharlal Nehru emphasized on friendly relations with the neighboring countries. The subsequent Prime Ministers of India especially I.K. Gujral had advocated in making of peaceful and friendly relations with the subcontinental countries. He had given a unique idea to foster bilateral relations with the neighbors. His idea is known as ‘Gujral Doctrine’. A dramatical change has been witnessed in Indian foreign policy since 1991.In the post-Cold War period, India’s national security has been vehemently threatened by terrorism, which originated from Pakistan-Afghanistan and partly Bangladesh. India has required a cooperative security, which can be made by mutual understanding among the South Asian countries. Additionally, the countries of South Asia need to evolve the concept of ‘Cooperative Security’ to explain the underlying logic of regional cooperation. According to C. Rajamohan, ‘cooperative security could be understood, as policies of governments, which see themselves as former adversaries or potential adversaries to shift from or avoid confrontationist policies.’ A cooperative security essentially reflects a policy of dealing peacefully with conflicts, not merely by abstention from violence or threats but by active engagement in negotiation, a search for practical solutions and with a commitment to preventive measures. Cooperative assumes the existence of a condition in which the two sides possess the military capabilities to harm each other. Establishing cooperative security runs into a complex process building confidence. South Asian nations often engaged with hostility to each other. Extra-regional powers have been influencing their powers in this region since a long time. South Asian nations are busy to purchase military equipment. In spite of weakened economic systems, these states are spending a huge amount of money for their security. India is the big power in this region in every aspect. The big states- small states syndrome is a negative factor in this respect. However, India will have to an initiative to extended ‘track II diplomacy’ or soft diplomacy for its security as well as the security of this region.Confidence building measures could help rejuvenate not only SAARC but also build trust and mutual confidence between India and its neighbors in South Asia. In this paper, I will focus on different aspects of India’s policy towards it, South-Asian neighbors. It will also be searched that how India is dealing with these countries by using a mixed type of diplomacy – both idealistic and realistic points of view. Security and cooperation are two major determinants of India’s foreign policy towards its South Asian neighbors.

Keywords: bilateral, diplomacy, infiltration, terrorism

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44 The Display of Age-Period/Age-Cohort Mortality Trends Using 1-Year Intervals Reveals Period and Cohort Effects Coincident with Major Influenza A Events

Authors: Maria Ines Azambuja

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Graphic displays of Age-Period-Cohort (APC) mortality trends generally uses data aggregated within 5 or 10-year intervals. Technology allows one to increase the amount of processed data. Displaying occurrences by 1-year intervals is a logic first step in the direction of attaining higher quality landscapes of variations in temporal occurrences. Method: 1) Comparison of UK mortality trends plotted by 10-, 5- and 1-year intervals; 2) Comparison of UK and US mortality trends (period X age and cohort X age) displayed by 1-year intervals. Source: Mortality data (period, 1x1, males, 1933-1912) uploaded from the Human Mortality Database to Excel files, where Period X Age and Cohort X Age graphics were produced. The choice of transforming age-specific trends from calendar to birth-cohort years (cohort = period – age) (instead of using cohort 1x1 data available at the HMD resource) was taken to facilitate the comparison of age-specific trends when looking across calendar-years and birth-cohorts. Yearly live births, males, 1933 to 1912 (UK) were uploaded from the HFD. Influenza references are from the literature. Results: 1) The use of 1-year intervals unveiled previously unsuspected period, cohort and interacting period x cohort effects upon all-causes mortality. 2) The UK and US figures showed variations associated with particular calendar years (1936, 1940, 1951, 1957-68, 72) and, most surprisingly, with particular birth-cohorts (1889-90 in the US, and 1900, 1918-19, 1940-41 and 1946-47, in both countries. Also, the figures showed ups and downs in age-specific trends initiated at particular birth-cohorts (1900, 1918-19 and 1947-48) or a particular calendar-year (1968, 1972, 1977-78 in the US), variations at times restricted to just a range of ages (cohort x period interacting effects). Importantly, most of the identified “scars” (period and cohort) correlates with the record of occurrences of Influenza A epidemics since the late 19th Century. Conclusions: The use of 1-year intervals to describe APC mortality trends both increases the amount of information available, thus enhancing the opportunities for patterns’ recognition, and increases our capability of interpreting those patterns by describing trends across smaller intervals of time (period or birth-cohort). The US and the UK mortality landscapes share many but not all 'scars' and distortions suggested here to be associated with influenza epidemics. Different size-effects of wars are evident, both in mortality and in fertility. But it would also be realistic to suppose that the preponderant influenza A viruses circulating in UK and US at the beginning of the 20th Century might be different and the difference to have intergenerational long-term consequences. Compared with the live births trend (UK data), birth-cohort scars clearly depend on birth-cohort sizes relatives to neighbor ones, which, if causally associated with influenza, would result from influenza-related fetal outcomes/selection. Fetal selection could introduce continuing modifications on population patterns of immune-inflammatory phenotypes that might give rise to 'epidemic constitutions' favoring the occurrence of particular diseases. Comparative analysis of mortality landscapes may help us to straight our record of past circulation of Influenza viruses and document associations between influenza recycling and fertility changes.

Keywords: age-period-cohort trends, epidemic constitution, fertility, influenza, mortality

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43 Designing Agile Product Development Processes by Transferring Mechanisms of Action Used in Agile Software Development

Authors: Guenther Schuh, Michael Riesener, Jan Kantelberg

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Due to the fugacity of markets and the reduction of product lifecycles, manufacturing companies from high-wage countries are nowadays faced with the challenge to place more innovative products within even shorter development time on the market. At the same time, volatile customer requirements have to be satisfied in order to successfully differentiate from market competitors. One potential approach to address the explained challenges is provided by agile values and principles. These agile values and principles already proofed their success within software development projects in the form of management frameworks like Scrum or concrete procedure models such as Extreme Programming or Crystal Clear. Those models lead to significant improvements regarding quality, costs and development time and are therefore used within most software development projects. Motivated by the success within the software industry, manufacturing companies have tried to transfer agile mechanisms of action to the development of hardware products ever since. Though first empirical studies show similar effects in the agile development of hardware products, no comprehensive procedure model for the design of development iterations has been developed for hardware development yet due to different constraints of the domains. For this reason, this paper focusses on the design of agile product development processes by transferring mechanisms of action used in agile software development towards product development. This is conducted by decomposing the individual systems 'product development' and 'agile software development' into relevant elements and symbiotically composing the elements of both systems in respect of the design of agile product development processes afterwards. In a first step, existing product development processes are described following existing approaches of the system theory. By analyzing existing case studies from industrial companies as well as academic approaches, characteristic objectives, activities and artefacts are identified within a target-, action- and object-system. In partial model two, mechanisms of action are derived from existing procedure models of agile software development. These mechanisms of action are classified in a superior strategy level, in a system level comprising characteristic, domain-independent activities and their cause-effect relationships as well as in an activity-based element level. Within partial model three, the influence of the identified agile mechanism of action towards the characteristic system elements of product development processes is analyzed. For this reason, target-, action- and object-system of the product development are compared with the strategy-, system- and element-level of agile mechanism of action by using the graph theory. Furthermore, the necessity of existence of activities within iteration can be determined by defining activity-specific degrees of freedom. Based on this analysis, agile product development processes are designed in form of different types of iterations within a last step. By defining iteration-differentiating characteristics and their interdependencies, a logic for the configuration of activities, their form of execution as well as relevant artefacts for the specific iteration is developed. Furthermore, characteristic types of iteration for the agile product development are identified.

Keywords: activity-based process model, agile mechanisms of action, agile product development, degrees of freedom

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42 Understanding the Construction of Social Enterprises in India: Through Identity and Context of Social Entrepreneurs

Authors: K. Bose

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India is one of the largest democracies in the global south, which demonstrates the highest social enterprise activities in the subcontinent. Although there has been a meteoric rise in social enterprise activities, it is not a new phenomenon, as it dates back to Vinoba Bhave's Land Gift movement in 1950. India also has a rich history of a welfare mix where non-governmental organisations played a significant role in the public welfare provision. Lately, the government’s impetus on entrepreneurship has contributed to a burgeoning social enterprise sector in the country; however, there is a lack in understanding of how social enterprises are constructed in India. Social entrepreneurship as practice has been conceptualised as a multi-dimensional concept, which is predominantly explained through the characteristics of a social entrepreneur. Social enterprise organisation, which is a component of social entrepreneurship practice are also classified through the role of the social entrepreneur; thus making social entrepreneur a vital unit shaping organisation and practice. Hence, individual identity of the social entrepreneur acts as a steering agent for defining organisation and practice. Individual identity does not operate in a vacuum and different isomorphic pressures (resource-rich actors/institutions) leads to negotiation in these identities. Dey and Teasdale's work investigated this identity work of non-profit practitioners within the practice of social enterprises in England. Furthermore, the construction of social enterprises is predominantly understood through two approaches i.e. an institutional logic perspective emerging from Europe and process and outcome perspective derived from the United States. These two approaches explain social enterprise as an inevitable institutional outcome in a linear and simplistic manner. Such linear institutional transition is inferred from structural policy reforms and austerity measures adopted by the government, which led to heightened competition for funds in the non-profit sector. These political and economic challenges were specific to the global north, which is different from transitions experienced in the global south, thus further investigation would help understand social enterprise activities as a contextual phenomenon. There is a growing interest in understanding the role of the context within the entrepreneurship literature, additionally, there is growing recognition in entrepreneurship research that economic behaviour is realised far better within its historical, temporal, institutional, spatial and social context, as these contexts provide boundaries to individuals in terms of opportunities and actions. Social enterprise phenomenon too is realised as contextual phenomenon though it differs from traditional entrepreneurship in terms of its dual mission (social and economic), however, the understanding of the role of context in social entrepreneurship has been limited. Hence, this work in progress study integrates identity work of social entrepreneur and the role of context. It investigates the identities of social entrepreneur and its negotiation within its context. Further, how this negotiated identity transcends into organisational practice in turn shaping how social enterprises are constructed in a specific region. The study employs a qualitative inquiry of semi-structured interviews and ethnographic institutionalism. Interviews were analysed using critical discourse analysis and the preliminary outcomes are currently a work in progress.

Keywords: context, Dey and Teasdale, identity, social entrepreneurs, social enterprise, social entrepreneurship

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41 A Randomised Controlled Trial and Process Evaluation of the Lifestart Parenting Programme

Authors: Sharon Millen, Sarah Miller, Laura Dunne, Clare McGeady, Laura Neeson

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This paper presents the findings from a randomised controlled trial (RCT) and process evaluation of the Lifestart parenting programme. Lifestart is a structured child-centred programme of information and practical activity for parents of children aged from birth to five years of age. It is delivered to parents in their own homes by trained, paid family visitors and it is offered to parents regardless of their social, economic or other circumstances. The RCT evaluated the effectiveness of the programme and the process evaluation documented programme delivery and included a qualitative exploration of parent and child outcomes. 424 parents and children participated in the RCT: 216 in the intervention group and 208 in the control group across the island of Ireland. Parent outcomes included: parental knowledge of child development, parental efficacy, stress, social support, parenting skills and embeddedness in the community. Child outcomes included cognitive, language and motor development and social-emotional and behavioural development. Both groups were tested at baseline (when children were less than 1 year old), mid-point (aged 3) and at post-test (aged 5). Data were collected during a home visit, which took two hours. The process evaluation consisted of interviews with parents (n=16 at baseline and end-point), and focus groups with Lifestart Coordinators (n=9) and Family Visitors (n=24). Quantitative findings from the RCT indicated that, compared to the control group, parents who received the Lifestart programme reported reduced parenting-related stress, increased knowledge of their child’s development, and improved confidence in their parenting role. These changes were statistically significant and consistent with the hypothesised pathway of change depicted in the logic model. There was no evidence of any change in parents’ embeddedness in the community. Although four of the five child outcomes showed small positive change for children who took part in the programme, these were not statistically significant and there is no evidence that the programme improves child cognitive and non-cognitive skills by immediate post-test. The qualitative process evaluation highlighted important challenges related to conducting trials of this magnitude and design in the general population. Parents reported that a key incentive to take part in study was receiving feedback from the developmental assessment, which formed part of the data collection. This highlights the potential importance of appropriate incentives in relation to recruitment and retention of participants. The interviews with intervention parents indicated that one of the first changes they experienced as a result of the Lifestart programme was increased knowledge and confidence in their parenting ability. The outcomes and pathways perceived by parents and described in the interviews are also consistent with the findings of the RCT and the theory of change underpinning the programme. This hypothesises that improvement in parental outcomes, arising as a consequence of the programme, mediate the change in child outcomes. Parents receiving the Lifestart programme reported great satisfaction with and commitment to the programme, with the role of the Family Visitor being identified as one of the key components of the programme.

Keywords: parent-child relationship, parental self-efficacy, parental stress, school readiness

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40 Mondoc: Informal Lightweight Ontology for Faceted Semantic Classification of Hypernymy

Authors: M. Regina Carreira-Lopez

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Lightweight ontologies seek to concrete union relationships between a parent node, and a secondary node, also called "child node". This logic relation (L) can be formally defined as a triple ontological relation (LO) equivalent to LO in ⟨LN, LE, LC⟩, and where LN represents a finite set of nodes (N); LE is a set of entities (E), each of which represents a relationship between nodes to form a rooted tree of ⟨LN, LE⟩; and LC is a finite set of concepts (C), encoded in a formal language (FL). Mondoc enables more refined searches on semantic and classified facets for retrieving specialized knowledge about Atlantic migrations, from the Declaration of Independence of the United States of America (1776) and to the end of the Spanish Civil War (1939). The model looks forward to increasing documentary relevance by applying an inverse frequency of co-ocurrent hypernymy phenomena for a concrete dataset of textual corpora, with RMySQL package. Mondoc profiles archival utilities implementing SQL programming code, and allows data export to XML schemas, for achieving semantic and faceted analysis of speech by analyzing keywords in context (KWIC). The methodology applies random and unrestricted sampling techniques with RMySQL to verify the resonance phenomena of inverse documentary relevance between the number of co-occurrences of the same term (t) in more than two documents of a set of texts (D). Secondly, the research also evidences co-associations between (t) and their corresponding synonyms and antonyms (synsets) are also inverse. The results from grouping facets or polysemic words with synsets in more than two textual corpora within their syntagmatic context (nouns, verbs, adjectives, etc.) state how to proceed with semantic indexing of hypernymy phenomena for subject-heading lists and for authority lists for documentary and archival purposes. Mondoc contributes to the development of web directories and seems to achieve a proper and more selective search of e-documents (classification ontology). It can also foster on-line catalogs production for semantic authorities, or concepts, through XML schemas, because its applications could be used for implementing data models, by a prior adaptation of the based-ontology to structured meta-languages, such as OWL, RDF (descriptive ontology). Mondoc serves to the classification of concepts and applies a semantic indexing approach of facets. It enables information retrieval, as well as quantitative and qualitative data interpretation. The model reproduces a triple tuple ⟨LN, LE, LT, LCF L, BKF⟩ where LN is a set of entities that connect with other nodes to concrete a rooted tree in ⟨LN, LE⟩. LT specifies a set of terms, and LCF acts as a finite set of concepts, encoded in a formal language, L. Mondoc only resolves partial problems of linguistic ambiguity (in case of synonymy and antonymy), but neither the pragmatic dimension of natural language nor the cognitive perspective is addressed. To achieve this goal, forthcoming programming developments should target at oriented meta-languages with structured documents in XML.

Keywords: hypernymy, information retrieval, lightweight ontology, resonance

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39 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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38 Deciphering Tumor Stroma Interactions in Retinoblastoma

Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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37 Dietetics Practice in the Scope of Disease Prevention in Community Settings: A School-Based Obesity Prevention Program

Authors: Elham Abbas Aljaaly, Nahlaa Abdulwahab Khalifa

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The active method of disease prevention is seen as the most affordable and sustainable action to deal with risks of non-communicable diseases such as obesity. This eight-week project aimed to pilot the feasibility and acceptability of a school-based programme, which is proposed to prevent and modify overweight status and possible related risk factors among student girls 'at the intermediate level' in Jeddah city. The programme was conducted through comprehensible approach targeting physical environment and school policies (nutritional/exercise/behavioural approach). The programme was designed to cultivate the personal and environmental awareness in schools for girls. This was applied by promoting healthy eating and physical activity through policies, physical education, healthier options for school canteens, and the creation of school health teams. The prevention programme was applied on 68 students (who agreed to participate) from grades 7th, 8th and 9th. A pre and post assessment questionnaire was employed on 66 students. The questionnaires were designed to obtain information on students' knowledge about health, nutrition and physical activity. Survey questions included information about nutrients, food consumption patterns, food intake and lifestyle. Physical education included training sessions for new opportunities for physical activities to be performed during school or after school hours. A running competition 'to enhance students’ performance for physical activities' was also conducted during the school visit. A visit to the school canteen was conducted to check, observe, record and assess all available food/beverage items and meals. The assessment method was a subjective method for the type of food/beverages if high in saturated fat, salt and sugar (HFSS) or non-HFSS. The school canteen administrators were encouraged to provide healthy food/beverage items and a sample healthy canteen was provided for implementation. Two healthy options were introduced to the school canteen. A follow up for students’ preferences for the introduced options and the purchasing power were assessed. Thirty-eight percent of young girls (n=26) were not participating in any form of physical activities inside or outside school. Skipping breakfast was stated by 42% (n=28) of students with no daily consumption (19%, n=13) for fruit/vegetables. Significant changes were noticed in students’ (n=66) overall responses to the pre and post questions (P value=.001). All students had participated in the conducted running competition sessions and reported satisfaction and enjoyment about the sessions. No absence was reported by the research team for attending physical education and activity sessions throughout the delivered programme. The purchasing power of the introduced healthy options of 'Salad and oatmeal' was increased to 18% in 8 weeks at the school canteen, and slightly affected the purchase for other less healthy options. The piloted programme indorsed better health and nutrition knowledge, healthy eating and lifestyle attitude, which could help young girls to obtain sustainable changes. It is expected that the outcomes of the programme will be a cornerstone for the futuristic national study that will assist policy makers and participants to build a knowledgeable health promotion scenario and make sure that school students have access to healthy foods, physical exercise and healthy lifestyle.

Keywords: adolescents, diet, exercise, behaviours, overweight/obesity, prevention-intervention programme, Saudi Arabia, schoolgirls

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36 Development and Validation of a Quantitative Measure of Engagement in the Analysing Aspect of Dialogical Inquiry

Authors: Marcus Goh Tian Xi, Alicia Chua Si Wen, Eunice Gan Ghee Wu, Helen Bound, Lee Liang Ying, Albert Lee

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The Map of Dialogical Inquiry provides a conceptual look at the underlying nature of future-oriented skills. According to the Map, learning is learner-oriented, with conversational time shifted from teachers to learners, who play a strong role in deciding what and how they learn. For example, in courses operating on the principles of Dialogical Inquiry, learners were able to leave the classroom with a deeper understanding of the topic, broader exposure to differing perspectives, and stronger critical thinking capabilities, compared to traditional approaches to teaching. Despite its contributions to learning, the Map is grounded in a qualitative approach both in its development and its application for providing feedback to learners and educators. Studies hinge on openended responses by Map users, which can be time consuming and resource intensive. The present research is motivated by this gap in practicality by aiming to develop and validate a quantitative measure of the Map. In addition, a quantifiable measure may also strengthen applicability by making learning experiences trackable and comparable. The Map outlines eight learning aspects that learners should holistically engage. This research focuses on the Analysing aspect of learning. According to the Map, Analysing has four key components: liking or engaging in logic, using interpretative lenses, seeking patterns, and critiquing and deconstructing. Existing scales of constructs (e.g., critical thinking, rationality) related to these components were identified so that the current scale could adapt items from. Specifically, items were phrased beginning with an “I”, followed by an action phrase, to fulfil the purpose of assessing learners' engagement with Analysing either in general or in classroom contexts. Paralleling standard scale development procedure, the 26-item Analysing scale was administered to 330 participants alongside existing scales with varying levels of association to Analysing, to establish construct validity. Subsequently, the scale was refined and its dimensionality, reliability, and validity were determined. Confirmatory factor analysis (CFA) revealed if scale items loaded onto the four factors corresponding to the components of Analysing. To refine the scale, items were systematically removed via an iterative procedure, according to their factor loadings and results of likelihood ratio tests at each step. Eight items were removed this way. The Analysing scale is better conceptualised as unidimensional, rather than comprising the four components identified by the Map, for three reasons: 1) the covariance matrix of the model specified for the CFA was not positive definite, 2) correlations among the four factors were high, and 3) exploratory factor analyses did not yield an easily interpretable factor structure of Analysing. Regarding validity, since the Analysing scale had higher correlations with conceptually similar scales than conceptually distinct scales, with minor exceptions, construct validity was largely established. Overall, satisfactory reliability and validity of the scale suggest that the current procedure can result in a valid and easy-touse measure for each aspect of the Map.

Keywords: analytical thinking, dialogical inquiry, education, lifelong learning, pedagogy, scale development

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35 Tailoring Workspaces for Generation Z: Harmonizing Teamwork, Privacy, and Connectivity

Authors: Maayan Nakash

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The modern workplace is undergoing a revolution, with Generation Z (Gen-Z) at the forefront of this transformative shift. However, empirical investigations specifically targeting the workplace preferences of this generation remain limited. Through direct examination of their tendencies via a survey approach, this study offers vital insights for aligning organizational policies and practices. The results presented in this paper are part of a comprehensive study that explored Gen Z's viewpoints on various employment market aspects, likely to decisively influence the design of future work environments. Data were collected via an online survey distributed among a cohort of 461 individuals from Gen-Z, born between the mid-1990s and 2010, consisting of 241 males (52.28%) and 220 females (47.72%). Responses were gauged using Likert scale statements that probed preferences for teamwork versus individual work, virtual versus personal interactions, and open versus private workspaces. Descriptive statistics and analytical analyses were conducted to pinpoint key patterns. We discovered that a high proportion of respondents (81.99%, n=378) exhibited a preference for teamwork over individual work. Correspondingly, the data indicate strong support for the recognition of team-based tasks as a tool contributing to personal and professional development. In terms of communication, the majority of respondents (61.38%) either disagreed (n=154) or slightly agreed (n=129) with the exclusive reliance on virtual interactions with their organizational peers. This finding underscores that despite technological progress, digital natives place significant value on physical interaction and non-mediated communication. Moreover, we understand that they also value a quiet and private work environment, clearly preferring it over open and shared workspaces. Considering that Gen-Z does not necessarily experience high levels of stress within social frameworks in the workplace, this can be attributed to a desire for a space that allows for focused engagement with work tasks. A One-Sample Chi-Square Test was performed on the observed distribution of respondents' reactions to each examined statement. The results showed statistically significant deviations from a uniform distribution (p<.001), indicating that the response patterns did not occur by chance and that there were meaningful tendencies in the participants' responses. The findings expand the theoretical knowledge base on human resources in the dynamics of a multi-generational workforce, illuminating the values, approaches, and expectations of Gen-Z. Practically, the results may lead organizations to equip themselves with tools to create policies tailored to Gen-Z in the context of workspaces and social needs, which could potentially foster a fertile environment and aid in attracting and retaining young talent. Future studies might include investigating potential mitigating factors, such as cultural influences or individual personality traits, which could further clarify the nuances in Gen-Z's work style preferences. Longitudinal studies tracking changes in these preferences as the generation matures may also yield valuable insights. Ultimately, as the landscape of the workforce continues to evolve, ongoing investigations into the unique characteristics and aspirations of emerging generations remain essential for nurturing harmonious, productive, and future-ready organizational environments.

Keywords: workplace, future of work, generation Z, digital natives, human resources management

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