Search results for: spent embryo medium

Authors: Hasmik V. Zanginyan, Gayane S. Ghazaryan, Laura M. Hovsepyan

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Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system that is induced in laboratory animals by developing an immune response against myelin epitopes. The typical clinical course is ascending palsy, which correlates with inflammation and tissue damage in the thoracolumbar spinal cord, although the optic nerves and brain (especially the subpial white matter and brainstem) are also often affected. With multiple sclerosis, there is a violation of lipid metabolism in myelin. When membrane lipids (glycosphingolipids, phospholipids) are disturbed, metabolites not only play a structural role in membranes but are also sources of secondary mediators that transmit multiple cellular signals. The purpose of this study was to investigate the effect of ganglioside as a therapeutic agent in experimental multiple sclerosis. The biological activity of a ganglioside-containing medicinal preparation (Cronassial) was evaluated in an experimental model of multiple sclerosis in laboratory animals. An experimental model of multiple sclerosis in rats was obtained by immunization with myelin basic protein (MBP), as well as homogenization of the spinal cord or brain. EAE was induced by administering a mixture of an encephalitogenic mixture (EGM) with Complete Freund’s Adjuvant. Mitochondrial fraction was isolated in a medium containing 0,25 M saccharose and 0, 01 M tris buffer, pH - 7,4, by a method of differential centrifugation on a K-24 centrifuge. Glutathione peroxidase activity was assessed by reduction reactions of hydrogen peroxide (H₂O₂) and lipid hydroperoxides (ROOH) in the presence of GSH. LPO activity was assessed by the amount of malondialdehyde (MDA) in the total homogenate and mitochondrial fraction of the spinal cord and brain of control and experimental autoimmune encephalomyelitis rats. MDA was assessed by a reaction with Thiobarbituric acid. For statistical data analysis on PNP, SPSS (Statistical Package for Social Science) package was used. The nature of the distribution of the obtained data was determined by the Kolmogorov-Smirnov criterion. The comparative analysis was performed using a nonparametric Mann-Whitney test. The differences were statistically significant when р ≤ 0,05 or р ≤ 0,01. Correlational analysis was conducted using a nonparametric Spearman test. In the work, refrigeratory centrifuge, spectrophotometer LKB Biochrom ULTROSPECII (Sweden), pH-meter PL-600 mrc (Israel), guanosine, and ATP (Sigma). The study of the process of lipid peroxidation in the total homogenate of the brain and spinal cord in experimental animals revealed an increase in the content of malonic dialdehyde. When applied, Cronassial observed normalization of lipid peroxidation processes. Reactive oxygen species, causing lipid peroxidation processes, can be toxic both for neurons and for oligodendrocytes that form myelin, causing a violation of their lipid composition. The high content of lipids in the brain and the uniqueness of their structure determines the nature of the development of LPO processes. The lipid layer of cellular and intracellular membranes performs two main functions -barrier and matrix (structural). Damage to the barrier leads to dysregulation of intracellular processes and severe disorders of cellular functions.

Keywords: experimental autoimmune encephalomyelitis, multiple sclerosis, neuroinflammation, therapy

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Authors: Muna Mitchell, Akshay Parchure, Krishna Singaraju

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There is an increasing need for medium- to long-span steel bridges with complex geometry due to site restrictions in developed areas. One of the solutions to grade separations in congested areas is to use longer spans on skewed supports that avoid at-grade obstructions limiting impacts to the foundation. Where vertical clearances are also a constraint, continuous steel girders can be used to reduce superstructure depths. Combining continuous long steel spans on severe skews can resolve the constraints at a cost. The behavior of skewed girders is challenging to analyze and design with subsequent complexity during fabrication and construction. As a part of a corridor improvement project, Walter P Moore designed two 1700-foot side-by-side bridges carrying four lanes of traffic in each direction over a railroad track. The bridges consist of prestressed concrete girder approach spans and three-span continuous steel plate girder units. The roadway design added complex geometry to the bridge with horizontal and vertical curves combined with superelevation transitions within the plate girder units. The substructure at the steel units was skewed approximately 56 degrees to satisfy the existing railroad right-of-way requirements. A horizontal point of curvature (PC) near the end of the steel units required the use flared girders and chorded slab edges. Due to the flared girder geometry, the cross-frame spacing in each bay is unique. Staggered cross frames were provided based on AASHTO LRFD and NCHRP guidelines for high skew steel bridges. Skewed steel bridges develop significant forces in the cross frames and rotation in the girder websdue to differential displacements along the girders under dead and live loads. In addition, under thermal loads, skewed steel bridges expand and contract not along the alignment parallel to the girders but along the diagonal connecting the acute corners, resulting in horizontal displacement both along and perpendicular to the girders. AASHTO LRFD recommends a 95 degree Fahrenheit temperature differential for the design of joints and bearings. The live load and the thermal loads resulted in significant horizontal forces and rotations in the bearings that necessitated the use of HLMR bearings. A unique bearing layout was selected to minimize the effect of thermal forces. The span length, width, skew, and roadway geometry at the bridges also required modular bridge joint systems (MBJS) with inverted-T bent caps to accommodate movement in the steel units. 2D and 3D finite element analysis models were developed to accurately determine the forces and rotations in the girders, cross frames, and bearings and to estimate thermal displacements at the joints. This paper covers the decision-making process for developing the framing plan, bearing configurations, joint type, and analysis models involved in the design of the high-skew three-span continuous steel plate girder bridges.

Keywords: complex geometry, continuous steel plate girders, finite element structural analysis, high skew, HLMR bearings, modular joint

Procedia PDF Downloads 196

Authors: Amber Dhoot, Tarush Gupta, Andrea Gurr, William Jenkins, Sandro Pietrunti, Alexis Tang

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Background: The COVID-19 pandemic has driven pharmacovigilance towards a new paradigm. Nowadays, more people than ever before are recognising and reporting adverse reactions from medications, treatments, and vaccines. In the modern era, with over 3.8 billion users, social media has become the most accessible medium for people to voice their opinions and so provides an opportunity to engage with more patient-centric and accessible pharmacovigilance. However, the pharmaceutical industry has been slow to incorporate social media into its modern pharmacovigilance strategy. This project aims to make social media a more effective tool in pharmacovigilance, and so reduce drug costs, improve drug safety and improve patient outcomes. This will be achieved by firstly uncovering and categorising the barriers facing the widespread adoption of social media in pharmacovigilance. Following this, the potential opportunities of social media will be explored. We will then propose realistic, practical recommendations to make social media a more effective tool for pharmacovigilance. Methodology: A comprehensive systematic literature review was conducted to produce a categorised summary of these barriers. This was followed by conducting 11 semi-structured interviews with pharmacovigilance experts to confirm the literature review findings whilst also exploring the unpublished and real-life challenges faced by those in the pharmaceutical industry. Finally, a survey of the general public (n = 112) ascertained public knowledge, perception, and opinion regarding the use of their social media data for pharmacovigilance purposes. This project stands out by offering perspectives from the public and pharmaceutical industry that fill the research gaps identified in the literature review. Results: Our results gave rise to several key analysis points. Firstly, inadequacies of current Natural Language Processing algorithms hinder effective pharmacovigilance data extraction from social media, and where data extraction is possible, there are significant questions over its quality. Social media also contains a variety of biases towards common drugs, mild adverse drug reactions, and the younger generation. Additionally, outdated regulations for social media pharmacovigilance do not align with new, modern General Data Protection Regulations (GDPR), creating ethical ambiguity about data privacy and level of access. This leads to an underlying mindset of avoidance within the pharmaceutical industry, as firms are disincentivised by the legal, financial, and reputational risks associated with breaking ambiguous regulations. Conclusion: Our project uncovered several barriers that prevent effective pharmacovigilance on social media. As such, social media should be used to complement traditional sources of pharmacovigilance rather than as a sole source of pharmacovigilance data. However, this project adds further value by proposing five practical recommendations that improve the effectiveness of social media pharmacovigilance. These include: prioritising health-orientated social media; improving technical capabilities through investment and strategic partnerships; setting clear regulatory guidelines using multi-stakeholder processes; creating an adverse drug reaction reporting interface inbuilt into social media platforms; and, finally, developing educational campaigns to raise awareness of the use of social media in pharmacovigilance. Implementation of these recommendations would speed up the efficient, ethical, and systematic adoption of social media in pharmacovigilance.

Keywords: adverse drug reaction, drug safety, pharmacovigilance, social media

Procedia PDF Downloads 83

Authors: Ding Liangxiao

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The technological advancements in Micro-Electro-Mechanical Systems (MEMS) have significantly contributed to the development of new, flexible capacitive pressure sensors,which are pivotal in transforming wearable and medical device technologies. This study employs the sophisticated simulation tools available in COMSOL Multiphysics® to develop and analyze a MEMS-based sensor with a tri-layered design. This sensor comprises top and bottom electrodes made from gold (Au), noted for their excellent conductivity, a middle dielectric layer made from a composite of Silver Nanowires (AgNWs) embedded in Thermoplastic Polyurethane (TPU), and a flexible, durable substrate of Polydimethylsiloxane (PDMS). This research was directed towards understanding how changes in the physical characteristics of the AgNWs/TPU dielectric layer—specifically, its thickness and surface area—impact the sensor's operational efficacy. We assessed several key electrical properties: capacitance, electric potential, and membrane displacement under varied pressure conditions. These investigations are crucial for enhancing the sensor's sensitivity and ensuring its adaptability across diverse applications, including health monitoring systems and dynamic user interface technologies. To ensure the reliability of our simulations, we applied the Effective Medium Theory to calculate the dielectric constant of the AgNWs/TPU composite accurately. This approach is essential for predicting how the composite material will perform under different environmental and operational stresses, thus facilitating the optimization of the sensor design for enhanced performance and longevity. Moreover, we explored the potential benefits of innovative three-dimensional structures for the dielectric layer compared to traditional flat designs. Our hypothesis was that 3D configurations might improve the stress distribution and optimize the electrical field interactions within the sensor, thereby boosting its sensitivity and accuracy. Our simulation protocol includes comprehensive performance testing under simulated environmental conditions, such as temperature fluctuations and mechanical pressures, which mirror the actual operational conditions. These tests are crucial for assessing the sensor's robustness and its ability to function reliably over extended periods, ensuring high reliability and accuracy in complex real-world environments. In our current research, although a full dynamic simulation analysis of the three-dimensional structures has not yet been conducted, preliminary explorations through three-dimensional modeling have indicated the potential for mechanical and electrical performance improvements over traditional planar designs. These initial observations emphasize the potential advantages and importance of incorporating advanced three-dimensional modeling techniques in the development of Micro-Electro-Mechanical Systems (MEMS)sensors, offering new directions for the design and functional optimization of future sensors. Overall, this study not only highlights the powerful capabilities of COMSOL Multiphysics® for modeling sophisticated electronic devices but also underscores the potential of innovative MEMS technology in advancing the development of more effective, reliable, and adaptable sensor solutions for a broad spectrum of technological applications.

Keywords: MEMS, flexible sensors, COMSOL Multiphysics, AgNWs/TPU, PDMS, 3D modeling, sensor durability

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Authors: Deon Bezuidenhout

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Pre-seeding with autologous endothelial cells improves the long-term patency of synthetic vascular grafts levels obtained with autografts, but is limited to a single centre due to resource, time and other constraints. Spontaneous in vivo endothelialization would obviate the need for pre-seeding, but has been shown to be absent in man due to limited transanastomotic and fallout healing, and the lack of transmural ingrowth due to insufficient porosity. Two types of graft scaffolds with increased interconnected porosity for improved tissue ingrowth and healing are thus proposed and described. Foam-type polyurethane (PU) scaffolds with small, medium and large, interconnected pores were made by phase inversion and spherical porogen extraction, with and without additional surface modification with covalently attached heparin and subsequent loading with and delivery of growth factors. Fibrillar scaffolds were made either by standard electrospinning using degradable PU (Degrapol®), or by dual electrospinning using non-degradable PU. The latter process involves sacrificial fibres that are co-spun with structural fibres and subsequently removed to increased porosity and pore size. Degrapol samples were subjected to in vitro degradation, and all scaffold types were evaluated in vivo for tissue ingrowth and vascularization using rat subcutaneous model. The foam scaffolds were additionally evaluated in a circulatory (rat infrarenal aortic interposition) model that allows for the grafts to be anastomotically and/or ablumenally isolated to discern and determine endothelialization mode. Foam-type grafts with large (150 µm) pores showed improved subcutaneous healing in terms of vascularization and inflammatory response over smaller pore sizes (60 and 90µm), and vascularization of the large porosity scaffolds was significantly increased by more than 70% by heparin modification alone, and by 150% to 400% when combined with growth factors. In the circulatory model, extensive transmural endothelialization (95±10% at 12 w) was achieved. Fallout healing was shown to be sporadic and limited in groups that were ablumenally isolated to prevent transmural ingrowth (16±30% wrapped vs. 80±20% control; p<0.002). Heparinization and GF delivery improved both mural vascularization and lumenal endothelialization. Degrapol electrospun scaffolds showed decrease in molecular mass and corresponding tensile strength over the first 2 weeks, but very little decrease in mass over the 4w test period. Studies on the effect of tissue ingrowth with and without concomitant degradation of the scaffolds, are being used to develop material models for the finite element modelling. In the case of the dual-spun scaffolds, the PU fibre fraction could be controlled shown to vary linearly with porosity (P = −0.18FF +93.5, r2=0.91), which in turn showed inverse linear correlation with tensile strength and elastic modulus (r2 > 0.96). Calculated compliance and burst pressures of the scaffolds increased with fibre fraction, and compliances matching the human popliteal artery (5-10 %/100 mmHg), and high burst pressures (> 2000 mmHg) could be achieved. Increasing porosity (76 to 82 and 90%) resulted in increased tissue ingrowth from 33±7 to 77±20 and 98±1% after 28d. Transmural endothelialization of highly porous foamed grafts is achievable in a circulatory model, and the enhancement of porosity and tissue ingrowth may hold the key the development of spontaneously endothelializing electrospun grafts.

Keywords: electrospinning, endothelialization, porosity, scaffold, vascular graft

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Authors: M. Mueller, M. Kuehn, M. Voelker

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In small and medium-sized enterprises (SMEs), the challenge is to create a well-grounded and reliable basis for process analysis, optimization and planning due to a lack of data. SMEs have limited access to methods with which they can effectively and efficiently analyse processes and identify cause-and-effect relationships in order to generate the necessary database and derive optimization potential from it. The implementation of digitalization within the framework of Industry 4.0 thus becomes a particular necessity for SMEs. For these reasons, the abstract presents an analysis methodology that is subject to the objective of developing an SME-appropriate methodology for efficient, temporarily feasible data collection and evaluation in flexible production and logistics systems as a basis for process analysis and optimization. The overall methodology focuses on retrospective, event-based tracing and analysis of material flow objects. The technological basis consists of Bluetooth low energy (BLE)-based transmitters, so-called beacons, and smart mobile devices (SMD), e.g. smartphones as receivers, between which distance data can be measured and derived motion profiles. The distance is determined using the Received Signal Strength Indicator (RSSI), which is a measure of signal field strength between transmitter and receiver. The focus is the development of a software-based methodology for interpretation of relative movements of transmitters and receivers based on distance data. The main research is on selection and implementation of pattern recognition methods for automatic process recognition as well as methods for the visualization of relative distance data. Due to an existing categorization of the database regarding process types, classification methods (e.g. Support Vector Machine) from the field of supervised learning are used. The necessary data quality requires selection of suitable methods as well as filters for smoothing occurring signal variations of the RSSI, the integration of methods for determination of correction factors depending on possible signal interference sources (columns, pallets) as well as the configuration of the used technology. The parameter settings on which respective algorithms are based have a further significant influence on result quality of the classification methods, correction models and methods for visualizing the position profiles used. The accuracy of classification algorithms can be improved up to 30% by selected parameter variation; this has already been proven in studies. Similar potentials can be observed with parameter variation of methods and filters for signal smoothing. Thus, there is increased interest in obtaining detailed results on the influence of parameter and factor combinations on data quality in this area. The overall methodology is realized with a modular software architecture consisting of independently modules for data acquisition, data preparation and data storage. The demonstrator for initialization and data acquisition is available as mobile Java-based application. The data preparation, including methods for signal smoothing, are Python-based with the possibility to vary parameter settings and to store them in the database (SQLite). The evaluation is divided into two separate software modules with database connection: the achievement of an automated assignment of defined process classes to distance data using selected classification algorithms and the visualization as well as reporting in terms of a graphical user interface (GUI).

Keywords: event-based tracing, machine learning, process classification, parameter settings, RSSI, signal smoothing

Procedia PDF Downloads 134

Authors: Emilio Galdeano-Gómez, Juan C. Pérez-Mesa, Laura Piedra-Muñoz, María C. García-Barranco, Jesús Hernández-Rubio

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The situation in which firms engage in simultaneous cooperation and competition with each other is a phenomenon known as co-opetition. This scenario has received increasing attention in business economics and management analyses. In the domain of supply chain networks and for small and medium-sized enterprises, SMEs, these strategies are of greater relevance given the complex environment of globalization and competition in open markets. These firms face greater challenges regarding technology and access to specific resources due to their limited capabilities and limited market presence. Consequently, alliances and collaborations with both buyers and suppliers prove to be key elements in overcoming these constraints. However, rivalry and competition are also regarded as major factors in successful internationalization processes, as they are drivers for firms to attain a greater degree of specialization and to improve efficiency, for example enabling them to allocate scarce resources optimally and providing incentives for innovation and entrepreneurship. The present work aims to contribute to the literature on SMEs’ internationalization strategies. The sample is constituted by a panel data of marketing firms from the Andalusian food sector and a multivariate regression analysis is developed, measuring variables of co-opetition and international activity. The hierarchical regression equations method has been followed, thus resulting in three estimated models: the first one excluding the variables indicative of channel type, while the latter two include the international retailer chain and wholesaler variable. The findings show that the combination of several factors leads to a complex scenario of inter-organizational relationships of cooperation and competition. In supply chain management analyses, these relationships tend to be classified as either buyer-supplier (vertical level) or supplier-supplier relationships (horizontal level). Several buyers and suppliers tend to participate in supply chain networks, and in which the form of governance (hierarchical and non-hierarchical) influences cooperation and competition strategies. For instance, due to their market power and/or their closeness to the end consumer, some buyers (e.g. large retailers in food markets) can exert an influence on the selection and interaction of several of their intermediate suppliers, thus endowing certain networks in the supply chain with greater stability. This hierarchical influence may in turn allow these suppliers to develop their capabilities (e.g. specialization) to a greater extent. On the other hand, for those suppliers that are outside these networks, this environment of hierarchy, characterized by a “hub firm” or “channel master”, may provide an incentive for developing their co-opetition relationships. These results prove that the analyzed firms have experienced considerable growth in sales to new foreign markets, mainly in Europe, dealing with large retail chains and wholesalers as main buyers. This supply industry is predominantly made up of numerous SMEs, which has implied a certain disadvantage when dealing with the buyers, as negotiations have traditionally been held on an individual basis and in the face of high competition among suppliers. Over recent years, however, cooperation among these marketing firms has become more common, for example regarding R&D, promotion, scheduling of production and sales.

Keywords: co-petition networks, international supply chain, maketing agrifood firms, SMEs strategies

Procedia PDF Downloads 80

Authors: Somnath Bhattacharyya

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

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

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Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

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Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.

Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

Procedia PDF Downloads 189

Authors: Sajad Khaliq Dar, Dipanjan Goswami, Arshad H. Khuroo, Mohd. Akhtar, Pulak Kumar Metia, Sudershan Kumar

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Background: Development of modified-release oral dosage formulations (OSD) like tacrolimus in narrow therapeutic categories, together with high levels of intra-individual variability, impose greater challenges. The risk assessment for bioequivalence studies requires developing a suitable design through pilot studies involving the comparison of multiple formulations of the same product with a marketed product to understand the in-vivo behaviour. These formulations could have varying coating levels and other minor quantitative differences to achieve the desired release rate for the final product. Although small-scale studies are critical before the conduct of full-scale Pharmacokinetic (PK) studies, regulatory agencies evaluate critical bioavailability attributes (CBA) before approving the submitted dossiers. Since Tacrolimus is a BCS Class II drug, therefore developing the extended-release formulation, in addition to associated challenges, provides an opportunity to present the In vitro-in vivo correlations (IVIVC) to regulatory agencies, not only to exhibit product quality but also to reduce the burden of additional human trials and cost involved to them for bringing the product to market. Objective: The objective of this study was to develop a Level-A In vitro - In vivo Correlation (IVIVC) model for Sun Pharma’s test formulation Tacrolimus ER tablet 4mg and extend its application to a widened dissolution window of 25% at 2.5 hours (critical release time) sampling time point. Experimental Procedure: Post the conduct of two in-vivo studies, a pilot study evaluating two test prototypes on 24 subjects (under fasting) and a pivotal study having 50 subjects (under fasting), the observed pharmacokinetic profile was used for IVIVC model development. The dissolution media used was 0.005% HPC + 0.25% SLS in Water 900 mL at pH 4.50 using USP II (Paddle) apparatus with alternative sinkers operated at 100 RPM. The sampling time points were chosen to mimic the drug absorption in vivo. The dissolution best fit to data was obtained using Makoid Banakar kinetics. Then deconvolution, anchoring to concepts of the single compartment by Wagner Nelson method was applied for tacrolimus slow-release formulation batch with film coating weight build-up of 5.4% (used in pilot bio study), medium release with Hypromellose (retard-release exhibit batch used in the pivotal study) and fast release formulation batch with film coating weight build-up of 5.05% (used in pilot bio study). Results and Conclusion: The results were deemed acceptable as prediction errors for internal and external validation were < 3% depicting in-vitro drug release mimics in-vivo absorption. Moreover, the prediction result for the Test/Reference ratio was <15% for all test formulations and widening dissolution (i.e., 39%-64% drug release at 2.5hrs) predictions were well within 80-125% when compared against Envarsus XR (reference drug). This IVIVC-validated model can be used in the futuristic exploration of dose titration with 1mg tacrolimus ER OSD as a surrogate for In-vivo bioequivalence trials.

Keywords: pharmacokinetics, BCS, oral dosage form, Bioavailability, intra-individual variability

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Authors: Carles Martinez-Almoyna Gual, Jiwon Choi

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Urban communities face risks of disintegration and segregation as a consequence of globalised migration processes towards urban environments. Linking social and cultural components with environmental and economic dimensions becomes the goal of all the disciplines that aim to shape more sustainable urban environments. Solutions require interdisciplinary approaches and the use of a complex array of tools. One of these tools is the implementation of urban farming, which provides a wide range of advantages for creating more inclusive spaces and integrated communities. Since food is strongly related to the values and identities of any cultural group, it can be used as a medium to promote social inclusion in the context of urban multicultural societies. By bringing people together into specific urban sites, food production can be integrated into multifunctional spaces while addressing social, economic and ecological goals. The goal of this research is to assess different approaches to urban agriculture by analysing three existing community gardens located in Newtown, a suburb of Wellington, New Zealand. As a context for developing research, Newtown offers different approaches to urban farming and is really valuable for observing current trends of socialization in diverse and multicultural societies. All three spaces are located on public land owned by Wellington City Council and confined to a small, complex and progressively denser urban area. The developed analysis was focused on social, cultural and physical dimensions, combining community engagement with different techniques of spatial assessment. At the same time, a detailed investigation of each community garden was conducted with comparative analysis methodologies. This multidirectional setting of the analysis was established for extracting from the case studies both specific and typological knowledge. Each site was analysed and categorised under three broad themes: people, space and food. The analysis revealed that all three case studies had really different spatial settings, different approaches to food production and varying profiles of supportive communities. The main differences identified were demographics, values, objectives, internal organization, appropriation, and perception of the space. The community gardens were approached as case studies for developing design research. Following participatory design processes with the different communities, the knowledge gained from the analysis was used for proposing changes in the physical environment. The end goal of the design research was to improve the capacity of the spaces to facilitate social inclusiveness. In order to generate tangible changes, a range of small, strategic and feasible spatial interventions was explored. The smallness of the proposed interventions facilitates implementation by reducing time frames, technical resources, funding needs, and legal processes, working within the community´s own realm. These small interventions are expected to be implemented over time as part of an ongoing collaboration between the different communities, the university, and the local council. The applied research methodology showcases the capacity of universities to develop civic engagement by working with real communities that have concrete needs and face overall threats of disintegration and segregation.

Keywords: community gardening, landscape architecture, participatory design, placemaking, social inclusion

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Authors: Liuhui Zhu, Peng Zeng

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With the rapid development in China, the urbanization has entered the transformation and promotion stage, and its direction of development has shifted to overall regional synergy. China has a large number of towns and villages, with comparative small scale and scattered distribution, which always support and provide resources to cities leading to urban-rural opposition, so it is difficult to achieve common development in a single town or village. In this context, the regional development should focus more on towns and villages to form a synergetic system, joining the regional association with cities. Thus, the paper raises the question about how to effectively organize towns and villages system to regulate the resource allocation and improve the comprehensive value of the regional area. To answer the question, it is necessary to find a suitable research unit and analysis of its present situation of towns and villages system for optimal development. By combing relevant researches and theoretical models, the county is the most basic administrative unit in China, which can directly guide and regulate the development of towns and villages, so the paper takes county as the research unit. Following the theoretical concept of ‘three structures and one network’, the paper concludes the research framework to analyse the present situation of towns and villages system, including scale structure, functional structure, spatial structure, and organization network. The analytical methods refer to the fractal theory and gravity model, using statistics and spatial data. The scale structure analyzes rank-size dimensions and uses the principal component method to calculate the comprehensive scale of towns and villages. The functional structure analyzes the functional types and industrial development of towns and villages. The spatial structure analyzes the aggregation dimension, network dimension, and correlation dimension of spatial elements to represent the overall spatial relationships. In terms of organization network, from the perspective of entity and ono-entity, the paper analyzes the transportation network and gravitational network. Based on the present situation analysis, the optimization strategies are proposed in order to achieve a synergetic relationship between towns and villages in the county area. The paper uses Suning county in the Beijing-Tianjin-Hebei region as a case study to apply the research framework and methods and then proposes the optimization orientations. The analysis results indicate that: (1) The Suning county is lack of medium-scale towns to transfer effect from towns to villages. (2) The distribution of gravitational centers is uneven, and the effect of gravity is limited only for nearby towns and villages. The gravitational network is not complete, leading to economic activities scattered and isolated. (3) The overall development of towns and villages system is immature, staying at ‘single heart and multi-core’ stage, and some specific optimization strategies are proposed. This study provides a regional view for the development of towns and villages and concludes the research framework and methods of towns and villages system for forming an effective synergetic relationship between them, contributing to organize resources and stimulate endogenous motivation, and form counter magnets to join the urban-rural integration.

Keywords: towns and villages system, organization structure, county area, fractal theory, gravity model

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

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

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

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Authors: Mohammad R. Aghakashkooli, Milutin G. Jovanovic

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The brushless doubly-fed reluctance generator (BDFRG) is an emerging, medium-speed alternative to a conventional wound rotor slip-ring doubly-fed induction generator (DFIG) in wind energy conversion systems (WECS). It can provide competitive overall performance and similar low failure rates of a typically 30% rated back-to-back power electronics converter in 2:1 speed ranges but with the following important reliability and cost advantages over DFIG: the maintenance-free operation afforded by its brushless structure, 50% synchronous speed with the same number of rotor poles (allowing the use of a more compact, and more efficient two-stage gearbox instead of a vulnerable three-stage one), and superior grid integration properties including simpler protection for the low voltage ride through compliance of the fractional converter due to the comparatively higher leakage inductances and lower fault currents. Vector controlled pulse-width-modulated converters generally feature a much lower total harmonic distortion relative to hysteresis counterparts with variable switching rates and as such have been a predominant choice for BDFRG (and DFIG) wind turbines. Eliminating a shaft position sensor, which is often required for control implementation in this case, would be desirable to address the associated reliability issues. This fact has largely motivated the recent growing research of sensorless methods and developments of various rotor position and/or speed estimation techniques for this purpose. The main limitation of all the observer-based control approaches for grid-connected wind power applications of the BDFRG reported in the open literature is the requirement for pre-commissioning procedures and prior knowledge of the machine inductances, which are usually difficult to accurately identify by off-line testing. A model reference adaptive system (MRAS) based sensor-less vector control scheme to be presented will overcome this shortcoming. The true machine parameter independence of the proposed field-oriented algorithm, offering robust, inherently decoupled real and reactive power control of the grid-connected winding, is achieved by on-line estimation of the inductance ratio, the underlying rotor angular velocity and position MRAS observer being reliant upon. Such an observer configuration will be more practical to implement and clearly preferable to the existing machine parameter dependent solutions, and especially bearing in mind that with very little modifications it can be adapted for commercial DFIGs with immediately obvious further industrial benefits and prospects of this work. The excellent encoder-less controller performance with maximum power point tracking in the base speed region will be demonstrated by realistic simulation studies using large-scale BDFRG design data and verified by experimental results on a small laboratory prototype of the WECS emulation facility.

Keywords: brushless doubly fed reluctance generator, model reference adaptive system, sensorless vector control, wind energy conversion

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Authors: Lam Hong Lan, Gabor Sarlos

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It is hard to search for best practices in promotion for local fashion brands in Vietnam as the industry is still very young. Local fashion start-ups have grown quickly in the last five years, thanks in part to the internet and social media. However, local designer/owners can face a huge challenge when competing with international brands in the Vietnamese market – and few local case studies are available for guidance. In response, this paper studied how local small- to medium-sized enterprises (SMEs) promote to their target customers in order to compete with international brands. Knowledge of both successful and unsuccessful approaches generated by this study is intended to both contribute to the academic literature on local fashion in Vietnam as well as to help local designers to learn from and improve their brand-building strategy. The primary study featured qualitative data collection via semi-structured depth interviews. Transcription and data analysis were conducted manually in order to identify success factors that local brands should consider as part of their promotion strategy. Purposive sampling of SMEs identified five designers in Ho Chi Minh City (the biggest city in Vietnam) and three designers in Hanoi (the second biggest) as interviewees. Participant attributes included: born in the 1980s or 1990s; familiar with internet and social media; designer/owner of a successful local fashion brand in the key middle market and/or mass market segments (which are crucial to the growth of local brands). A secondary study was conducted using social listening software to gather further qualitative data on what were considered to be successful or unsuccessful approaches to local fashion brand promotion on social media. Both the primary and secondary studies indicated that local designers had maximized their promotion budget by using owned media and earned media instead of paid media. Findings from the qualitative interviews indicate that internet and social media have been used as effective promotion platforms by local fashion start-ups. Facebook and Instagram were the most popular social networks used by the SMEs interviewed, and these social platforms were believed to offer a more affordable promotional strategy than traditional media such as TV and/or print advertising. Online stores were considered an important factor in helping the SMEs to reach customers beyond the physical store. Furthermore, a successful online store allowed some SMEs to reduce their business rental costs by maintaining their physical store in a cheaper, less central city area as opposed to a more traditional city center store location. In addition, the small comparative size of the SMEs allowed them to be more attentive to their customers, leading to higher customer satisfaction and rate of return. In conclusion, this study found that these kinds of cost savings helped the SMEs interviewed to focus their scarce resources on producing unique, high-quality collections in order to differentiate themselves from international brands. Facebook and Instagram were the main platforms used for promotion and brand-building. The main challenge to this promotion strategy identified by the SMEs interviewed was to continue to find innovative ways to maximize the impact of a limited marketing budget.

Keywords: Vietnam, SMEs, fashion brands, promotion, marketing, social listening

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Authors: Arifur Rahman, Ardeshir Amirkhani, Honghua Hu, Mark Molloy, Karen Vickery

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Introduction and Objectives: Staphylococcus aureus and coagulase-negative staphylococci comprises approximately 65% of infections associated with medical devices and are well known for their biofilm formatting ability. Biofilm-related infections are extremely difficult to eradicate owing to their high tolerance to antibiotics and host immune defences. Currently, there is no efficient method for early biofilm detection. A better understanding to enable detection of biofilm specific proteins in vitro and in vivo can be achieved by studying planktonic and different growth phases of biofilms using a proteome analysis approach. Our goal was to construct a reference map of planktonic and biofilm associated proteins of S. aureus. Methods: S. aureus reference strain (ATCC 25923) was used to grow 24 hours planktonic, 3-day wet biofilm (3DWB), and 12-day wet biofilm (12DWB). Bacteria were grown in tryptic soy broth (TSB) liquid medium. Planktonic growth was used late logarithmic bacteria, and the Centres for Disease Control (CDC) biofilm reactor was used to grow 3 days, and 12-day hydrated biofilms, respectively. Samples were subjected to reduction, alkylation and digestion steps prior to Multiplex labelling using Tandem Mass Tag (TMT) 10-plex reagent (Thermo Fisher Scientific). The labelled samples were pooled and fractionated by high pH RP-HPLC which followed by loading of the fractions on a nanoflow UPLC system (Eksigent UPLC system, AB SCIEX). Mass spectrometry (MS) data were collected on an Orbitrap Elite (Thermo Fisher Scientific) Mass Spectrometer. Protein identification and relative quantitation of protein levels were performed using Proteome Discoverer (version 1.3, Thermo Fisher Scientific). After the extraction of protein ratios with Proteome Discoverer, additional processing, and statistical analysis was done using the TMTPrePro R package. Results and Discussion: The present study showed that a considerable proteomic difference exists among planktonic and biofilms from S. aureus. We identified 1636 total extracellular secreted proteins, of which 350 and 137 proteins of 3DWB and 12DWB showed significant abundance variation from planktonic preparation, respectively. Of these, simultaneous up-regulation in between 3DWB and 12DWB proteins such as extracellular matrix-binding protein ebh, enolase, transketolase, triosephosphate isomerase, chaperonin, peptidase, pyruvate kinase, hydrolase, aminotransferase, ribosomal protein, acetyl-CoA acetyltransferase, DNA gyrase subunit A, glycine glycyltransferase and others we found in this biofilm producer. On the contrary, simultaneous down-regulation in between 3DWB and 12DWB proteins such as alpha and delta-hemolysin, lipoteichoic acid synthase, enterotoxin I, serine protease, lipase, clumping factor B, regulatory protein Spx, phosphoglucomutase, and others also we found in this biofilm producer. In addition, we also identified a big percentage of hypothetical proteins including unique proteins. Therefore, a comprehensive knowledge of planktonic and biofilm associated proteins identified by S. aureus will provide a basis for future studies on the development of vaccines and diagnostic biomarkers. Conclusions: In this study, we constructed an initial reference map of planktonic and various growth phase of biofilm associated proteins which might be helpful to diagnose biofilm associated infections.

Keywords: bacterial biofilms, CDC bioreactor, S. aureus, mass spectrometry, TMT

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Authors: Francisco J. Ortega, Claudia Roman, Moisés García-Morales, Francisco J. Navarro

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Asphaltic bitumen has been largely used in both industrial and civil engineering, mostly in pavement construction and roofing membrane manufacture. However, bitumen as such is greatly susceptible to temperature variations, and dramatically changes its in-service behavior from a viscoelastic liquid, at medium-high temperatures, to a brittle solid at low temperatures. Bitumen modification prevents these problems and imparts improved performance. Isocyanates like polymeric MDI (mixture of 4,4′-diphenylmethane di-isocyanate, 2,4’ and 2,2’ isomers, and higher homologues) have shown to remarkably enhance bitumen properties at the highest in-service temperatures expected. This comes from the reaction between the –NCO pendant groups of the oligomer and the most polar groups of asphaltenes and resins in bitumen. In addition, oxygen diffusion and/or UV radiation may provoke bitumen hardening and ageing. With the purpose of minimizing these effects, nano-layered-silicates (nanoclays) are increasingly being added to bitumen formulations. Montmorillonites, a type of naturally occurring mineral, may produce a nanometer scale dispersion which improves bitumen thermal, mechanical and barrier properties. In order to increase their lipophilicity, these nanoclays are normally treated so that organic cations substitute the inorganic cations located in their intergallery spacing. In the present work, the combined effect of polymeric MDI and the commercial montmorillonite Cloisite® 20A was evaluated. A selected bitumen with penetration within the range 160/220 was modified with 10 wt.% Cloisite® 20A and 2 wt.% polymeric MDI, and the resulting ternary composites were characterized by linear rheology, X-ray diffraction (XRD) and Atomic Force Microscopy (AFM). The rheological tests evidenced a notable solid-like behavior at the highest temperatures studied when bitumen was just loaded with 10 wt.% Cloisite® 20A and high-shear blended for 20 minutes. However, if polymeric MDI was involved, the sequence of addition exerted a decisive control on the linear rheology of the final ternary composites. Hence, in bitumen/Cloisite® 20A/polymeric MDI formulations, the previous solid-like behavior disappeared. By contrast, an inversion in the order of addition (bitumen/polymeric MDI/ Cloisite® 20A) enhanced further the solid-like behavior imparted by the nanoclay. In order to gain a better understanding of the factors that govern the linear rheology of these ternary composites, a morphological and microstructural characterization based on XRD and AFM was conducted. XRD demonstrated the existence of clay stacks intercalated by bitumen molecules to some degree. However, the XRD technique cannot provide detailed information on the extent of nanoclay delamination, unless the entire fraction has effectively been fully delaminated (situation in which no peak is observed). Furthermore, XRD was unable to provide precise knowledge neither about the spatial distribution of the intercalated/exfoliated platelets nor about the presence of other structures at larger length scales. In contrast, AFM proved its power at providing conclusive information on the morphology of the composites at the nanometer scale and at revealing the structural modification that yielded the rheological properties observed. It was concluded that high-shear blending brought about a nanoclay-reinforced network. As for the bitumen/Cloisite® 20A/polymeric MDI formulations, the solid-like behavior was destroyed as a result of the agglomeration of the nanoclay platelets promoted by chemical reactions.

Keywords: Atomic Force Microscopy, bitumen, composite, isocyanate, montmorillonite.

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Authors: Mariana Stuparu-Cretu, Doina-Carina Voinescu, Rodica-Mihaela Dinica, Daniela Borda, Camelia Vizireanu, Gabriela Iordachescu, Camelia Busila

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Obesity is involved in the etiology or acceleration of progression of important non-communicable diseases, such as: metabolic, cardiovascular, rheumatological, oncological and depression. It is a need to prevent the obesity occurrence, like a key link in disease management. From this point of view, the best approach is to early educate youngsters upon the need for a healthy nutrition lifestyle associated with constant physical activities. The objective of the study was to assess correlations between weight condition, physical activities and food preferences of students from South East Romania. Questionnaires were applied on high school students in Galati: 1006 girls and 880 boys, aged between 14 and 19 years (being approved by Local School Inspectorate and the Ethics Committee of the 'Dunarea de Jos' University of Galati). The collected answers have been statistically processed by using the multivariate regression method (PLS2) by Unscramble X program (Camo, Norway). Multiple variables such as age group, body mass index, nutritional habits and physical activities were separately analysed, depending on gender and general mathematical models were proposed to explain the obesity trend at an early age. The study results show that overweight and obesity are present in less than a fifth of the adolescents who were surveyed. With a very small variation and a strong correlation of over 86% for 99% of the cases, a general preference for sweet foods, nocturnal eating associated with computer work and a reduced period of physical activity is noticed for girls. In addition, the overweight girls consume sweet juices and alcohol, although a percentage of them also practice the gym. There is also a percentage of the normoponderal girls that consume high caloric foods which predispose this group to turn into overweight cases in time. Within the studied group, statistics for the boys show a positive correlation of almost 87% for over 96% of cases. They prefer high calories foods, fast food, and sweet juices, and perform medium physical activities. Both overweight and underweight boys are more sedentary. Over 15% of girls and over a quarter of boys consume alcohol. All these bad eating habits seem to increase with age, for both sexes. To conclude, obesity and overweight assessed in adolescents in S-E Romania reveal nonsignificant percentage differences between boys and girls. However, young people in this area of the country are sedentary in general; a significant percentage prefers sweets / sweet juices / fast-food and practice computer nourishing. The authors consider that at this age, it is very useful to adapt nutritional education by new methods of food processing and market supply. This would require an early understanding of the difference among foods and nutrients and the benefits of physical activities integrated into the healthy current lifestyle, as a measure for preventing and managing non-communicable chronic diseases related to nutritional errors and sedentarism. Acknowledgment— This study has been partial founded by the Francophone University Agency, Project Réseau régional dans le domaine de la santé, la nutrition et la sécurité alimentaire (SaIN), no.21899/ 06.09.2017.

Keywords: adolescents, body mass index, nutritional habits, obesity, physical activity

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Authors: Martin Cvek, Miroslav Mrlik, Michal Sedlacik, Tomas Plachy

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Magnetorheological elastomers (MREs) are multi-phase composite materials containing micron-sized ferromagnetic particles dispersed in an elastomeric matrix. Their properties such as modulus, damping, magneto-striction, and electrical conductivity can be controlled by an external magnetic field and/or pressure. These features of the MREs are used in the development of damping devices, shock attenuators, artificial muscles, sensors or active elements of electric circuits. However, imperfections on the particle/matrix interfaces result in the lower performance of the MREs when compared with theoretical values. Moreover, magnetic particles are susceptible to corrosion agents such as acid rains or sea humidity. Therefore, the modification of particles is an effective tool for the improvement of MRE performance due to enhanced compatibility between particles and matrix as well as improvements of their thermo-oxidation and chemical stability. In this study, the carbonyl iron (CI) particles were controllably modified with poly(trimethylsilyloxyethyl methacrylate) (PHEMATMS) nano-grafts to develop magnetic core–shell structures exhibiting proper wetting with various elastomeric matrices resulting in improved performance within a frame of rheological, magneto-piezoresistance, pressure-piezoresistance, or radio-absorbing properties. The desired molecular weight of PHEMATMS nano-grafts was precisely tailored using surface-initiated atom transfer radical polymerization (ATRP). The CI particles were firstly functionalized using a 3-aminopropyltriethoxysilane agent, followed by esterification reaction with α-bromoisobutyryl bromide. The ATRP was performed in the anisole medium using ethyl α-bromoisobutyrate as a macroinitiator, N, N´, N´´, N´´-pentamethyldiethylenetriamine as a ligand, and copper bromide as an initiator. To explore the effect PHEMATMS molecular weights on final properties, two variants of core-shell structures with different nano-graft lengths were synthesized, while the reaction kinetics were designed through proper reactant feed ratios and polymerization times. The PHEMATMS nano-grafts were characterized by nuclear magnetic resonance and gel permeation chromatography proving information to their monomer conversions, molecular chain lengths, and low polydispersity indexes (1.28 and 1.35) as the results of the executed ATRP. The successful modifications were confirmed via Fourier transform infrared- and energy-dispersive spectroscopies while expected wavenumber outputs and element presences, respectively, of constituted PHEMATMS nano-grafts, were occurring in the spectra. The surface morphology of bare CI and their PHEMATMS-grafted analogues was further studied by scanning electron microscopy, and the thicknesses of grafted polymeric layers were directly observed by transmission electron microscopy. The contact angles as a measure of particle/matrix compatibility were investigated employing the static sessile drop method. The PHEMATMS nano-grafts enhanced compatibility of hydrophilic CI with low-surface-energy hydrophobic polymer matrix in terms of their wettability and dispersibility in an elastomeric matrix. Thus, the presence of possible defects at the particle/matrix interface is reduced, and higher performance of modified MREs is expected.

Keywords: atom transfer radical polymerization, core-shell, particle modification, wettability

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Authors: Sarah M. Schoellhammer, Stephen Gibb

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Bureaucracy, in particular, its core element, a formal and stable hierarchy of authority, is proving less and less appropriate under the conditions of today’s knowledge economy. Centralization and formalization were consistently found to hinder innovation, undermining cross-functional collaboration, personal responsibility, and flexibility. With its focus on systematical planning, controlling and monitoring the development of new or improved solutions for customers, even innovation management as a discipline is to a significant extent based on a mechanistic understanding of organizations. The most important drivers of innovation, human creativity, and initiative, however, can be more hindered than supported by central elements of classic innovation management, such as predefined innovation strategies, rigid stage gate processes, and decisions made in management gate meetings. Heterarchy, as an alternative network form of organization, is essentially characterized by its dynamic influence structures, whereby the biggest influence is allocated by the collective to the persons perceived the most competent in a certain issue. Theoretical arguments that the non-hierarchical concept better supports innovation than bureaucracy have been supported by empirical research. These prior studies either focus on the structure and general functioning of non-hierarchical organizations or on their innovativeness, that means innovation as an outcome. Complementing classic innovation management approaches, this work aims to shed light on how innovations are initiated and realized in heterarchies in order to identify alternative solutions practiced under conditions of the post-bureaucratic organization. Through an initial individual case study, which is part of a multiple-case project, the innovation practices of an innovative and highly heterarchical medium-sized company in the German fire engineering industry are investigated. In a pragmatic mixed methods approach media resonance, company documents, and workspace architecture are analyzed, in addition to qualitative interviews with the CEO and employees of the case company, as well as a quantitative survey aiming to characterize the company along five scaled dimensions of a heterarchy spectrum. The analysis reveals some similarities and striking differences to approaches suggested by classic innovation management. The studied heterarchy has no predefined innovation strategy guiding new product and service development. Instead, strategic direction is provided by the CEO, described as visionary and creative. Procedures for innovation are hardly formalized, with new product ideas being evaluated on the basis of gut feeling and flexible, rather general criteria. Employees still being hesitant to take responsibility and make decisions, hierarchical influence is still prominent. Described as open-minded and collaborative, culture and leadership were found largely congruent with definitions of innovation culture. Overall, innovation efforts at the case company tend to be coordinated more through cultural than through formal organizational mechanisms. To better enable innovation in mainstream organizations, responsible practitioners are recommended not to limit changes to reducing the central elements of the bureaucratic organization, formalization, and centralization. The freedoms this entails need to be sustained through cultural coordination mechanisms, with personal initiative and responsibility by employees as well as common innovation-supportive norms and values. These allow to integrate diverse competencies, opinions, and activities and, thus, to guide innovation efforts.

Keywords: bureaucracy, heterarchy, innovation management, values

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Authors: Camille Aouinaït, Danilo Christen, Christoph Carlen

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Introduction: Small and Medium-sized Enterprises (SMEs) are facing different challenges such as pressures on environmental resources, the rise of downstream power, and trade liberalization. Remaining competitive by implementing innovations and engaging in collaborations could be a strategic solution. In Switzerland, the Federal Institute for Research in Agriculture (Agroscope), the Federal schools of technology (EPFL and ETHZ), Cantonal universities and Universities of Applied Sciences (UAS) can provide substantial inputs. UAS were developed with specific missions to match the labor markets and society needs. Research projects produce patents, publications and improved networks of scientific expertise. The study’s goal is to measure the contribution of UAS and research organization to innovation and the impact of collaborations with partners in the non-academic environment in Swiss traditional fruit production. Materials and methods: The European projects Traditional Food Network to improve the transfer of knowledge for innovation (TRAFOON) and Social Impact Assessment of Productive Interactions between science and society (SIAMPI) frame the present study. The former aims to fill the gap between the needs of traditional food producing SMEs and innovations implemented following European projects. The latter developed a method to assess the impacts of scientific research. On one side, interviews with market players have been performed to make an inventory of needs of Swiss SMEs producing apricots and berries. The participative method allowed matching the current needs and the existing innovations coming from past European projects. Swiss stakeholders (e.g. producers, retailers, an inter-branch organization of fruits and vegetables) directly rated the needs on a five-Likert scale. To transfer the knowledge to SMEs, training workshops have been organized for apricot and berries actors separately, on specific topics. On the other hand, a mapping of a social network is drawn to characterize the links between actors, with a focus on the Swiss canton of Valais and UAS Valais Wallis. Type and frequency of interactions among actors have identified thanks to interviews. Preliminary results: A list of 369 SMEs needs grouped in 22 categories was produced with 37 fulfilled questionnaires. Swiss stakeholders rated 31 needs very important. Training workshops on apricot are focusing on varietal innovations, storage, disease (bacterial blight), pest (Drosophila suzukii), sorting and rootstocks. Entrepreneurship was targeted through trademark discussions in berry production. The UAS Valais Wallis collaborated on a few projects with Agroscope along with industries, at European and national levels. Political and public bodies interfere with the central area of agricultural vulgarization that induces close relationships between the research and the practical side. Conclusions: The needs identified by Swiss stakeholders are becoming part of training workshops to incentivize innovations. The UAS Valais Wallis takes part in collaboration projects with the research environment and market players that bring innovations helping SMEs in their contextual environment. Then, a Strategic Research and Innovation Agenda will be created in order to pursue research and answer the issues facing by SMEs.

Keywords: agriculture, innovation, knowledge transfer, university and research collaboration

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Authors: Z. A. Al Marhoon, H. S. Al Ramis, C. Teodoriu

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Well-integrity is one of the major elements considered for drilling geothermal, oil, and gas wells. Well-integrity is minimizing the risk of unplanned fluid flow in the well bore throughout the well lifetime. Well integrity is maximized by applying technical concepts along with practical practices and strategic planning. These practices are usually governed by standardization and regulation entities. Practices during well construction can affect the integrity of the seal at the time of abandonment. On the other hand, achieving a perfect barrier system is impracticable due to the needed cost. This results in a needed balance between regulations requirements and practical applications. The guidelines are only effective when they are attainable in practical applications. Various governmental regulations and international standards have different guidelines on what constitutes high-quality isolation from unwanted flow. Each regulating or standardization body differ in requirements based on the abandonment objective. Some regulation account more for the environmental impact, water table contamination, and possible leaks. Other regulation might lean towards driving more economical benefits while achieving an acceptable isolation criteria. The research methodology used in this topic is derived from a literature review method combined with a compare and contrast analysis. The literature review on various zonal isolation regulations and standards has been conducted. A review includes guidelines from NORSOK (Norwegian governing entity), BSEE (USA offshore governing entity), API (American Petroleum Institute) combined with ISO (International Standardization Organization). The compare and contrast analysis is conducted by assessing the objective of each abandonment regulations and standardization. The current state of well barrier regulation is in balancing action. From one side of this balance, the environmental impact and complete zonal isolation is considered. The other side of the scale is practical application and associated cost. Some standards provide a fair amount of details concerning technical requirements and are often flexible with the needed associated cost. These guidelines cover environmental impact with laws that prevent major or disastrous environmental effects of improper sealing of wells. Usually these regulations are concerned with the near future of sealing rather than long-term. Consequently, applying these guidelines become more feasible from a cost point of view to the required plugging entities. On the other hand, other regulation have well integrity procedures and regulations that lean toward more restrictions environmentally with an increased associated cost requirements. The environmental impact is detailed and covered with its entirety, including medium to small environmental impact in barrier installing operations. Clear and precise attention to long-term leakage prevention is present in these regulations. The result of the compare and contrast analysis of the literature showed that there are various objectives that might tip the scale from one side of the balance (cost) to the other (sealing quality) especially in reference to zonal isolation. Furthermore, investing in initial well construction is a crucial part of ensuring safe final well abandonment. The safety and the cost saving at the end of the well life cycle is dependent upon a well-constructed isolation systems at the beginning of the life cycle. Long term studies on zonal isolation using various hydraulic or mechanical materials need to take place to further assess permanently abandoned wells to achieve the desired balance. Well drilling and isolation techniques will be more effective when they are operationally feasible and have reasonable associated cost to aid the local economy.

Keywords: plug and abandon, P&A regulation, P&A standards, international guidelines, gap analysis

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Authors: Annis Lai Chu Fung

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While aggression had high stability throughout developmental stages and across generations, it should be the top priority of researchers and frontline helping professionals to develop prevention and intervention programme for aggressive children and children at risk of developing aggressive behaviours. Although there is a substantial amount of anti-bullying programmes, they gave disappointingly small effect sizes. The neglectful practical significance could be attributed to the overly simplistic categorisation of individuals involved as bullies or victims. In the past three decades, the distinction between reactive and proactive aggression has been well-proved. As children displaying reactively aggressive behaviours have distinct social-information processing pattern with those showing proactively aggressive behaviours, it is critical to identify the unique needs of the two subtypes accordingly when designing an intervention. The onset of reactive aggression and proactive aggression was observed at earliest in 4.4 and 6.8 years old respectively. Such findings called for a differential early intervention targeting these high-risk children. However, to the best of the author’s knowledge, the author was the first to establish an evidence-based intervention programme against reactive and proactive aggression. With the largest samples in the world, the author, in the past 10 years, explored three different approaches and their effectiveness against aggression quantitatively and qualitatively with longitudinal design. The three approaches presented are (a) cognitive-behavioral approach, (b) moral education, with Chinese marital arts and ethics as the medium, and (c) bioneurological measures (omega-3 supplementation). The studies adopted a multi-informant approach with repeated measures before and after the intervention, and follow-up assessment. Participants were recruited from primary and secondary schools in Hong Kong. In the cognitive-behavioral approach, 66 reactive aggressors and 63 proactive aggressors, aged from 11 to 17, were identified from 10,096 secondary-school children with questionnaire and subsequent structured interview. Participants underwent 10 group sessions specifically designed for each subtype of aggressor. Results revealed significant declines in aggression levels from the baseline to the follow-up assessment after 1 year. In moral education through the Chinese martial arts, 315 high-risk aggressive children, aged 6 to 12 years, were selected from 3,511 primary-school children and randomly assigned into four types of 10-session intervention group, namely martial-skills-only, martial-ethics-only, both martial-skills-and-ethics, and physical fitness (placebo). Results showed only the martial-skills-and-ethics group had a significant reduction in aggression after treatment and 6 months after treatment comparing with the placebo group. In the bioneurological approach, 218 children, aged from 8 to 17, were randomly assigned to the omega-3 supplement group and the placebo group. Results revealed that compared with the placebo group, the omega-3 supplement group had significant declines in aggression levels at the 6-month follow-up assessment. All three approaches were effective in reducing proactive and reactive aggression. Traditionally, intervention programmes against aggressive behaviour often adapted the cognitive and/or behavioural approach. However, cognitive-behavioural approach for children was recently challenged by its demanding requirement of cognitive ability. Traditional cognitive interventions may not be as beneficial to an older population as in young children. The present study offered an insightful perspective in aggression reduction measures.

Keywords: intervention, outcome effectiveness, proactive aggression, reactive aggression

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Authors: Eduardo Rodrigues, Gisela Mendes, José M. Torres, José E. Sousa

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In the sequence of the liberalisation of the electricity sector a progressive engagement of consumers has been considered and targeted by sector regulatory policies. With the objective of promoting market competition while protecting consumers interests, by transferring some of the upstream benefits to the end users while reaching a fair distribution of system costs, different market models to value consumers’ demand flexibility at the energy community level are envisioned. Local Energy and Flexibility Markets (LEFM) involve stakeholders interested in providing or procure local flexibility for community, services and markets’ value. Under the scope of DOMINOES, a European research project supported by Horizon 2020, the local market concept developed is expected to: • Enable consumers/prosumers empowerment, by allowing them to value their demand flexibility and Distributed Energy Resources (DER); • Value local liquid flexibility to support innovative distribution grid management, e.g., local balancing and congestion management, voltage control and grid restoration; • Ease the wholesale market uptake of DER, namely small-scale flexible loads aggregation as Virtual Power Plants (VPPs), facilitating Demand Response (DR) service provision; • Optimise the management and local sharing of Renewable Energy Sources (RES) in Medium Voltage (MV) and Low Voltage (LV) grids, trough energy transactions within an energy community; • Enhance the development of energy markets through innovative business models, compatible with ongoing policy developments, that promote the easy access of retailers and other service providers to the local markets, allowing them to take advantage of communities’ flexibility to optimise their portfolio and subsequently their participation in external markets. The general concept proposed foresees a flow of market actions, technical validations, subsequent deliveries of energy and/or flexibility and balance settlements. Since the market operation should be dynamic and capable of addressing different requests, either prioritising balancing and prosumer services or system’s operation, direct procurement of flexibility within the local market must also be considered. This paper aims to highlight the research on the definition of suitable DR models to be used by the Distribution System Operator (DSO), in case of technical needs, and by the retailer, mainly for portfolio optimisation and solve unbalances. The models to be proposed and implemented within relevant smart distribution grid and microgrid validation environments, are focused on day-ahead and intraday operation scenarios, for predictive management and near-real-time control respectively under the DSO’s perspective. At local level, the DSO will be able to procure flexibility in advance to tackle different grid constrains (e.g., demand peaks, forecasted voltage and current problems and maintenance works), or during the operating day-to-day, to answer unpredictable constraints (e.g., outages, frequency deviations and voltage problems). Due to the inherent risks of their active market participation retailers may resort to DR models to manage their portfolio, by optimising their market actions and solve unbalances. The interaction among the market actors involved in the DR activation and in flexibility exchange is explained by a set of sequence diagrams for the DR modes of use from the DSO and the energy provider perspectives. • DR for DSO’s predictive management – before the operating day; • DR for DSO’s real-time control – during the operating day; • DR for retailer’s day-ahead operation; • DR for retailer’s intraday operation.

Keywords: demand response, energy communities, flexible demand, local energy and flexibility markets

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Authors: Monique M. Keller, Roline Barnes, Corlia Brandt

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Introduction Scientific evidence on the hand forces and the types of grasps measurement during daily tasks are lacking, leaving a gap in the field of hand rehabilitation and robotics. Measuring the grasp forces and types produced by the individual fingers during daily functional tasks is valuable to inform and grade rehabilitation practices for second to fifth metacarpal fractures with robust scientific evidence. Feix et al, 2016 identified the most extensive and complete grasp study that resulted in the GRASP taxonomy. Covid-19 virus changed data collection across the globe and safety precautions in research are essential to ensure the health of participants and researchers. Methodology A cross-sectional study investigated six healthy adults aged 20 to 59 years, pilot participants’ hand forces during 105 tasks. The tasks were categorized into five sections namely, personal care, transport and moving around, home environment and inside, gardening and outside, and office. The predominant grasp of each task was identified guided by the GRASP Taxonomy. Grasp forces were measured with 13mm force-sensing resistors glued onto a glove attached to each of the dominant and non-dominant hand’s individual fingers. Testing equipment included Flexiforce 13millimetres FSR .5" circle, calibrated prior to testing, 10k 1/4w resistors, Arduino pro mini 5.0v – compatible, Esp-01-kit, Arduino uno r3 – compatible board, USB ab cable - 1m, Ftdi ft232 mini USB to serial, Sil 40 inline connectors, ribbon cable combo male header pins, female to female, male to female, two gloves, glue to attach the FSR to glove, Arduino software programme downloaded on a laptop. Grip strength measurements with Jamar dynamometer prior to testing and after every 25 daily tasks were taken to will avoid fatigue and ensure reliability in testing. Covid-19 precautions included wearing face masks at all times, screening questionnaires, temperatures taken, wearing surgical gloves before putting on the testing gloves 1.5 metres long wires attaching the FSR to the Arduino to maintain social distance. Findings Predominant grasps observed during 105 tasks included, adducted thumb (17), lateral tripod (10), prismatic three fingers (12), small diameter (9), prismatic two fingers (9), medium wrap (7), fixed hook (5), sphere four fingers (4), palmar (4), parallel extension (4), index finger extension (3), distal (3), power sphere (2), tripod (2), quadpod (2), prismatic four fingers (2), lateral (2), large-diameter (2), ventral (2), precision sphere (1), palmar pinch (1), light tool (1), inferior pincher (1), and writing tripod (1). Range of forces applied per category, personal care (1-25N), transport and moving around (1-9 N), home environment and inside (1-41N), gardening and outside (1-26.5N), and office (1-20N). Conclusion Scientifically measurements of finger forces with careful consideration to types of grasps used in daily tasks should guide rehabilitation practices and robotic design to ensure a return to the full participation of the individual into the community.

Keywords: activities of daily living (ADL), Covid-19, force-sensing resistors, grasps, hand forces

Procedia PDF Downloads 190

Authors: Enya Trenholm-Jensen

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This paper employs various semiotic methodologies to examine the mechanism of soft power. Soft power refers to a country’s global reputation and their ability to leverage that reputation to achieve certain aims. South Korea has invested heavily in their soft power strategy for a multitude of predominantly historical and geopolitical reasons. On account of this investment and the global prominence of their strategy, South Korea was considered to be the optimal candidate for the aims of this investigation. Having isolated the entertainment industry as one of the most heavily funded segments of the South Korean soft power strategy, the analysis restricted itself to this sector. Within this industry, two entertainment products were selected as case studies. The case studies were chosen based on commercial success according to metrics such as streams, purchases, and subsequent revenue. This criterion was deemed to be the most objective and verifiable indicator of the products general appeal. The entertainment products which met the chosen criterion were Netflix’ “Squid Game” and BTS’ hit single “Butter”. The methodologies employed were chosen according to the medium of the entertainment products. For “Squid Game,” an aesthetic analysis was carried out to investigate how multi- layered meanings were mobilized in a show popularized by its visual grammar. To examine “Butter”, both music semiology and linguistic analysis were employed. The music section featured an analysis underpinned by denotative and connotative music semiotic theories borrowing from scholars Theo van Leeuwen and Martin Irvine. The linguistic analysis focused on stance and semantic fields according to scholarship by George Yule and John W. DuBois. The aesthetic analysis of the first case study revealed intertextual references to famous artworks, which served to augment the emotional provocation of the Squid Game narrative. For the second case study, the findings exposed a set of musical meaning units arranged in a patchwork of familiar and futuristic elements to achieve a song that existed on the boundary between old and new. The linguistic analysis of the song’s lyrics found a deceptively innocuous surface level meaning that bore implications for authority, intimacy, and commercial success. Whether through means of visual metaphor, embedded auditory associations, or linguistic subtext, the collective findings of the three analyses exhibited a desire to conjure a form of positive arousal in the spectator. In the synthesis section, this process is likened to that of branding. Through an exploration of branding, the entertainment products can be understood as cogs in a larger operation aiming to create positive associations to Korea as a country and a concept. Limitations in the form of a timeframe biased perspective are addressed, and directions for future research are suggested. This paper employs semiotic methodologies to examine two entertainment products as mechanisms of soft power. Through means of visual metaphor, embedded auditory associations, or linguistic subtext, the findings reveal a desire to conjure positive arousal in the spectator. The synthesis finds similarities to branding, thus positioning the entertainment products as cogs in a larger operation aiming to create positive associations to Korea as a country and a concept.

Keywords: BTS, cognitive semiotics, entertainment, soft power, south korea, squid game

Procedia PDF Downloads 154

Authors: Agnieszka E. Laudy, Karolina Stępien, Sergiusz Lulinski, Krzysztof Durka, Stefan Tyski

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1,3-dihydro-1-hydroxy-2,1-benzoxaborole and its derivatives are a particularly interesting group of synthetic agents and were successfully employed in supramolecular chemistry medicine. The first important compounds, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole and 5-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole were identified as potent antifungal agents. In contrast, (S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride is in the second phase of clinical trials as a drug for the treatment of Gram-negative bacterial infections of the Enterobacteriaceae family and Pseudomonas aeruginosa. Equally important and difficult task is to search for compounds active against Gram-negative bacilli, which have multi-drug-resistance efflux pumps actively removing many of the antibiotics from bacterial cells. We have examined whether halogen-substituted benzoxaborole-based derivatives and their analogues possess antibacterial activity and are substrates for multi-drug-resistance efflux pumps. The antibacterial activity of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole and 10 halogen-substituted its derivatives, as well as 1,2-phenylenediboronic acid and 3 synthesised fluoro-substituted its analogs, were evaluated. The activity against the reference strains of Gram-positive (n=5) and Gram-negative bacteria (n=10) was screened by the disc-diffusion test (0.4 mg of tested compounds was applied onto paper disc). The minimal inhibitory concentration values and the minimal bactericidal concentration values were estimated according to The Clinical and Laboratory Standards Institute and The European Committee on Antimicrobial Susceptibility Testing recommendations. During the minimal inhibitory concentration values determination with or without phenylalanine-arginine beta-naphthylamide (50 mg/L) efflux pump inhibitor, the concentrations of tested compounds ranged 0.39-400 mg/L in the broth medium supplemented with 1 mM magnesium sulfate. Generally, the studied benzosiloxaboroles and benzoxadiboroles showed a higher activity against Gram-positive cocci than against Gram-negative rods. Moreover, benzosiloxaboroles have the higher activity than benzoxadiboroles compounds. In this study, we demonstrated that substitution (mono-, di- or tetra-) of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole with halogen groups resulted in an increase in antimicrobial activity as compared to the parent substance. Interestingly, the 6,7-dichloro-substituted parent substance was found to be the most potent against Gram-positive cocci: Staphylococcus sp. (minimal inhibitory concentration 6.25 mg/L) and Enterococcus sp. (minimal inhibitory concentration 25 mg/L). On the other hand, mono- and dichloro-substituted compounds were the most actively removed by efflux pumps present in Gram-negative bacteria mainly from Enterobacteriaceae family. In the presence of efflux pump inhibitor the minimal inhibitory concentration values of chloro-substituted benzosiloxaboroles decreased from 400 mg/L to 3.12 mg/L. Of note, the highest increase in bacterial susceptibility to tested compounds in the presence of phenylalanine-arginine beta-naphthylamide was observed for 6-chloro-, 6,7-dichloro- and 6,7-difluoro-substituted benzosiloxaboroles. In the case of Escherichia coli, Enterobacter cloacae and P. aeruginosa strains at least a 32-fold decrease in the minimal inhibitory concentration values of these agents were observed. These data demonstrate structure-activity relationships of the tested derivatives and highlight the need for further search for benzoxaboroles and related compounds with significant antimicrobial properties. Moreover, the influence of phenylalanine-arginine beta-naphthylamide on the susceptibility of Gram-negative rods to studied benzosiloxaboroles indicate that some tested agents are substrates for efflux pumps in Gram-negative rods.

Keywords: antibacterial activity, benzosiloxaboroles, efflux pumps, phenylalanine-arginine beta-naphthylamide

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Authors: Artur Tyliszczak, Ewa Szymanek, Maciej Marek

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Flow through granular materials is important to a vast array of industries, for instance in construction industry where granular layers are used for bulkheads and isolators, in chemical engineering and catalytic reactors where large surfaces of packed granular beds intensify chemical reactions, or in energy production systems, where granulates are promising materials for heat storage and heat transfer media. Despite the common usage of granulates and extensive research performed in this field, phenomena occurring between granular solid elements or between solids and fluid are still not fully understood. In the present work we analyze the heat exchange process between the flowing medium (gas, liquid) and solid material inside the granular layers. We consider them as a composite of isolated solid elements and inter-granular spaces in which a gas or liquid can flow. The structure of the layer is controlled by shapes of particular granular elements (e.g., spheres, cylinders, cubes, Raschig rings), its spatial distribution or effective characteristic dimension (total volume or surface area). We will analyze to what extent alteration of these parameters influences on flow characteristics (turbulent intensity, mixing efficiency, heat transfer) inside the layer and behind it. Analysis of flow inside granular layers is very complicated because the use of classical experimental techniques (LDA, PIV, fibber probes) inside the layers is practically impossible, whereas the use of probes (e.g. thermocouples, Pitot tubes) requires drilling of holes inside the solid material. Hence, measurements of the flow inside granular layers are usually performed using for instance advanced X-ray tomography. In this respect, theoretical or numerical analyses of flow inside granulates seem crucial. Application of discrete element methods in combination with the classical finite volume/finite difference approaches is problematic as a mesh generation process for complex granular material can be very arduous. A good alternative for simulation of flow in complex domains is an immersed boundary-volume penalization (IB-VP) in which the computational meshes have simple Cartesian structure and impact of solid objects on the fluid is mimicked by source terms added to the Navier-Stokes and energy equations. The present paper focuses on application of the IB-VP method combined with large eddy simulation (LES). The flow solver used in this work is a high-order code (SAILOR), which was used previously in various studies, including laminar/turbulent transition in free flows and also for flows in wavy channels, wavy pipes and over various shape obstacles. In these cases a formal order of approximation turned out to be in between 1 and 2, depending on the test case. The current research concentrates on analyses of the flows in dense granular layers with elements distributed in a deterministic regular manner and validation of the results obtained using LES-IB method and body-fitted approach. The comparisons are very promising and show very good agreement. It is found that the size, number of elements and their distribution have huge impact on the obtained results. Ordering of the granular elements (or lack of it) affects both the pressure drop and efficiency of the heat transfer as it significantly changes mixing process.

Keywords: granular layers, heat transfer, immersed boundary method, numerical simulations

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Authors: Denis V. Axenov-Gribanov, Irina V. Voytsekhovskaya, Evgenii S. Protasov, Maxim A. Timofeyev

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Isolated ecosystems existing under specific environmental conditions have been shown to be promising sources of new strains of actinobacteria. The taiga forest of Baikal Siberia has not been well studied, and its actinobacterial population remains uncharacterized. The proximity between the huge water mass of Lake Baikal and high mountain ranges influences the structure and diversity of the plant world in Siberia. Here, we report the isolation of eighteen actinobacterial strains from male cones of Pinus sylvestris trees growing on the shore of the ancient Lake Baikal in Siberia. The actinobacterial strains were isolated on solid nutrient MS media and Czapek agar supplemented with cycloheximide and phosphomycin. Identification of actinobacteria was carried out by 16S rRNA gene sequencing and further analysis of the evolutionary history. Four different liquid and solid media (NL19, DNPM, SG and ISP) were tested for metabolite production. The metabolite extracts produced by the isolated strains were tested for antibacterial and antifungal activities. Also, antiradical activity of crude extracts was carried out. Strain Streptomyces sp. IB 2014 I 74-3 that active against Gram-negative bacteria was selected for dereplication analysis with using the high-yield liquid chromatography with mass-spectrometry. Mass detection was performed in both positive and negative modes, with the detection range set to 160–2500 m/z. Data were collected and analyzed using Bruker Compass Data Analysis software, version 4.1. Dereplication was performed using the Dictionary of Natural Products (DNP) database version 6.1 with the following search parameters: accurate molecular mass, absorption spectra and source of compound isolation. Thus, in addition to more common representative strains of Streptomyces, several species belonging to the genera Rhodococcus, Amycolatopsis, and Micromonospora were isolated. Several of the selected strains were deposited in the Russian Collection of Agricultural Microorganisms (RCAM), St. Petersburg, Russia. All isolated strains exhibited antibacterial and antifungal activities. We identified several strains that inhibited the growth of the pathogen Candida albicans but did not hinder the growth of Saccharomyces cerevisiae. Several isolates were active against Gram-positive and Gram-negative bacteria. Moreover, extracts of several strains demonstrated high antioxidant activity. The high proportion of biologically active strains producing antibacterial and specific antifungal compounds may reflect their role in protecting pollen against phytopathogens. Dereplication of the secondary metabolites of the strain Streptomyces sp. IB 2014 I 74-3 was resulted in the fact that a total of 59 major compounds were detected in the culture liquid extract of strain cultivated in ISP medium. Eight compounds were preliminarily identified based on characteristics described in the Dictionary of Natural Products database, using the search parameters Streptomyces sp. IB 2014 I 74-3 was found to produce saframycin A, Y3 and S; 2-amino-3-oxo-3H-phenoxazine-1,8-dicarboxylic acid; galtamycinone; platencin A4-13R and A4-4S; ganefromycin d1; the antibiotic SS 8201B; and streptothricin D, 40-decarbamoyl, 60-carbamoyl. Moreover, forty-nine of the 59 compounds detected in the extract examined in the present study did not result in any positive hits when searching within the DNP database and could not be identified based on available mass-spec data. Thus, these compounds might represent new findings.

Keywords: actinobacteria, Baikal Lake, biodiversity, male cones, Pinus sylvestris

Procedia PDF Downloads 234