Search results for: ADME properties
Commenced in January 2007
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Edition: International
Paper Count: 8979

Search results for: ADME properties

69 Polysaccharide Polyelectrolyte Complexation: An Engineering Strategy for the Development of Commercially Viable Sustainable Materials

Authors: Jeffrey M. Catchmark, Parisa Nazema, Caini Chen, Wei-Shu Lin

Abstract:

Sustainable and environmentally compatible materials are needed for a wide variety of volume commercial applications. Current synthetic materials such as plastics, fluorochemicals (such as PFAS), adhesives and resins in form of sheets, laminates, coatings, foams, fibers, molded parts and composites are used for countless products such as packaging, food handling, textiles, biomedical, construction, automotive and general consumer devices. Synthetic materials offer distinct performance advantages including stability, durability and low cost. These attributes are associated with the physical and chemical properties of these materials that, once formed, can be resistant to water, oils, solvents, harsh chemicals, salt, temperature, impact, wear and microbial degradation. These advantages become disadvantages when considering the end of life of these products which generate significant land and water pollution when disposed of and few are recycled. Agriculturally and biologically derived polymers offer the potential of remediating these environmental and life-cycle difficulties, but face numerous challenges including feedstock supply, scalability, performance and cost. Such polymers include microbial biopolymers like polyhydroxyalkanoates and polyhydroxbutirate; polymers produced using biomonomer chemical synthesis like polylactic acid; proteins like soy, collagen and casein; lipids like waxes; and polysaccharides like cellulose and starch. Although these materials, and combinations thereof, exhibit the potential for meeting some of the performance needs of various commercial applications, only cellulose and starch have both the production feedstock volume and cost to compete with petroleum derived materials. Over 430 million tons of plastic is produced each year and plastics like low density polyethylene cost ~$1500 to $1800 per ton. Over 400 million tons of cellulose and over 100 million tons of starch are produced each year at a volume cost as low as ~$500 to $1000 per ton with the capability of increased production. Cellulose and starches, however, are hydroscopic materials that do not exhibit the needed performance in most applications. Celluloses and starches can be chemically modified to contain positive and negative surface charges and such modified versions of these are used in papermaking, foods and cosmetics. Although these modified polysaccharides exhibit the same performance limitations, recent research has shown that composite materials comprised of cationic and anionic polysaccharides in polyelectrolyte complexation exhibit significantly improved performance including stability in diverse environments. Moreover, starches with added plasticizers can exhibit thermoplasticity, presenting the possibility of improved thermoplastic starches when comprised of starches in polyelectrolyte complexation. In this work, the potential for numerous volume commercial products based on polysaccharide polyelectrolyte complexes (PPCs) will be discussed, including the engineering design strategy used to develop them. Research results will be detailed including the development and demonstration of starch PPC compositions for paper coatings to replace PFAS; adhesives; foams for packaging, insulation and biomedical applications; and thermoplastic starches. In addition, efforts to demonstrate the potential for volume manufacturing with industrial partners will be discussed.

Keywords: biomaterials engineering, commercial materials, polysaccharides, sustainable materials

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

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

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

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

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

Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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

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

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66 Analytical Model of Locomotion of a Thin-Film Piezoelectric 2D Soft Robot Including Gravity Effects

Authors: Zhiwu Zheng, Prakhar Kumar, Sigurd Wagner, Naveen Verma, James C. Sturm

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Soft robots have drawn great interest recently due to a rich range of possible shapes and motions they can take on to address new applications, compared to traditional rigid robots. Large-area electronics (LAE) provides a unique platform for creating soft robots by leveraging thin-film technology to enable the integration of a large number of actuators, sensors, and control circuits on flexible sheets. However, the rich shapes and motions possible, especially when interacting with complex environments, pose significant challenges to forming well-generalized and robust models necessary for robot design and control. In this work, we describe an analytical model for predicting the shape and locomotion of a flexible (steel-foil-based) piezoelectric-actuated 2D robot based on Euler-Bernoulli beam theory. It is nominally (unpowered) lying flat on the ground, and when powered, its shape is controlled by an array of piezoelectric thin-film actuators. Key features of the models are its ability to incorporate the significant effects of gravity on the shape and to precisely predict the spatial distribution of friction against the contacting surfaces, necessary for determining inchworm-type motion. We verified the model by developing a distributed discrete element representation of a continuous piezoelectric actuator and by comparing its analytical predictions to discrete-element robot simulations using PyBullet. Without gravity, predicting the shape of a sheet with a linear array of piezoelectric actuators at arbitrary voltages is straightforward. However, gravity significantly distorts the shape of the sheet, causing some segments to flatten against the ground. Our work includes the following contributions: (i) A self-consistent approach was developed to exactly determine which parts of the soft robot are lifted off the ground, and the exact shape of these sections, for an arbitrary array of piezoelectric voltages and configurations. (ii) Inchworm-type motion relies on controlling the relative friction with the ground surface in different sections of the robot. By adding torque-balance to our model and analyzing shear forces, the model can then determine the exact spatial distribution of the vertical force that the ground is exerting on the soft robot. Through this, the spatial distribution of friction forces between ground and robot can be determined. (iii) By combining this spatial friction distribution with the shape of the soft robot, in the function of time as piezoelectric actuator voltages are changed, the inchworm-type locomotion of the robot can be determined. As a practical example, we calculated the performance of a 5-actuator system on a 50-µm thick steel foil. Piezoelectric properties of commercially available thin-film piezoelectric actuators were assumed. The model predicted inchworm motion of up to 200 µm per step. For independent verification, we also modelled the system using PyBullet, a discrete-element robot simulator. To model a continuous thin-film piezoelectric actuator, we broke each actuator into multiple segments, each of which consisted of two rigid arms with appropriate mass connected with a 'motor' whose torque was set by the applied actuator voltage. Excellent agreement between our analytical model and the discrete-element simulator was shown for both for the full deformation shape and motion of the robot.

Keywords: analytical modeling, piezoelectric actuators, soft robot locomotion, thin-film technology

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65 Numerical Analysis of Mandible Fracture Stabilization System

Authors: Piotr Wadolowski, Grzegorz Krzesinski, Piotr Gutowski

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The aim of the presented work is to recognize the impact of mini-plate application approach on the stress and displacement within the stabilization devices and surrounding bones. The mini-plate osteosynthesis technique is widely used by craniofacial surgeons as an improved replacement of wire connection approach. Many different types of metal plates and screws are used to the physical connection of fractured bones. Below investigation is based on a clinical observation of patient hospitalized with mini-plate stabilization system. Analysis was conducted on a solid mandible geometry, which was modeled basis on the computed tomography scan of the hospitalized patient. In order to achieve most realistic connected system behavior, the cortical and cancellous bone layers were assumed. The temporomandibular joint was simplified to the elastic element to allow physiological movement of loaded bone. The muscles of mastication system were reduced to three pairs, modeled as shell structures. Finite element grid was created by the ANSYS software, where hexahedral and tetrahedral variants of SOLID185 element were used. A set of nonlinear contact conditions were applied on connecting devices and bone common surfaces. Properties of particular contact pair depend on screw - mini-plate connection type and possible gaps between fractured bone around osteosynthesis region. Some of the investigated cases contain prestress introduced to the mini-plate during the application, what responds the initial bending of the connecting device to fit the retromolar fossa region. Assumed bone fracture occurs within the mandible angle zone. Due to the significant deformation of the connecting plate in some of the assembly cases the elastic-plastic model of titanium alloy was assumed. The bone tissues were covered by the orthotropic material. As a loading were used the gauge force of magnitude of 100N applied in three different locations. Conducted analysis shows significant impact of mini-plate application methodology on the stress distribution within the miniplate. Prestress effect introduces additional loading, which leads to locally exceed the titanium alloy yield limit. Stress in surrounding bone increases rapidly around the screws application region, exceeding assumed bone yield limit, what indicate the local bone destruction. Approach with the doubled mini-plate shows increased stress within the connector due to the too rigid connection, where the main path of loading leads through the mini-plates instead of plates and connected bones. Clinical observations confirm more frequent plate destruction of stiffer connections. Some of them could be an effect of decreased low cyclic fatigue capability caused by the overloading. The executed analysis prove that the mini-plate system provides sufficient support to mandible fracture treatment, however, many applicable solutions shifts the entire system to the allowable material limits. The results show that connector application with the initial loading needs to be carefully established due to the small material capability tolerances. Comparison to the clinical observations allows optimizing entire connection to prevent future incidents.

Keywords: mandible fracture, mini-plate connection, numerical analysis, osteosynthesis

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64 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach

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

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63 Green Architecture from the Thawing Arctic: Reconstructing Traditions for Future Resilience

Authors: Nancy Mackin

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Historically, architects from Aalto to Gaudi to Wright have looked to the architectural knowledge of long-resident peoples for forms and structural principles specifically adapted to the regional climate, geology, materials availability, and culture. In this research, structures traditionally built by Inuit peoples in a remote region of the Canadian high Arctic provides a folio of architectural ideas that are increasingly relevant during these times of escalating carbon emissions and climate change. ‘Green architecture from the Thawing Arctic’ researches, draws, models, and reconstructs traditional buildings of Inuit (Eskimo) peoples in three remote, often inaccessible Arctic communities. Structures verified in pre-contact oral history and early written history are first recorded in architectural drawings, then modeled and, with the participation of Inuit young people, local scientists, and Elders, reconstructed as emergency shelters. Three full-sized building types are constructed: a driftwood and turf-clad A-frame (spring/summer); a stone/bone/turf house with inwardly spiraling walls and a fan-shaped floor plan (autumn); and a parabolic/catenary arch-shaped dome from willow, turf, and skins (autumn/winter). Each reconstruction is filmed and featured in a short video. Communities found that the reconstructed buildings and the method of involving young people and Elders in the reconstructions have on-going usefulness, as follows: 1) The reconstructions provide emergency shelters, particularly needed as climate change worsens storms, floods, and freeze-thaw cycles and scientists and food harvesters who must work out of the land become stranded more frequently; 2) People from the communities re-learned from their Elders how to use materials from close at hand to construct impromptu shelters; 3) Forms from tradition, such as windbreaks at entrances and using levels to trap warmth within winter buildings, can be adapted and used in modern community buildings and housing; and 4) The project initiates much-needed educational and employment opportunities in the applied sciences (engineering and architecture), construction, and climate change monitoring, all offered in a culturally-responsive way. Elders, architects, scientists, and young people added innovations to the traditions as they worked, thereby suggesting new sustainable, culturally-meaningful building forms and materials combinations that can be used for modern buildings. Adding to the growing interest in bio-mimicry, participants looked at properties of Arctic and subarctic materials such as moss (insulation), shrub bark (waterproofing), and willow withes (parabolic and catenary arched forms). ‘Green Architecture from the Thawing Arctic’ demonstrates the effective, useful architectural oeuvre of a resilient northern people. The research parallels efforts elsewhere in the world to revitalize long-resident peoples’ architectural knowledge, in the interests of designing sustainable buildings that reflect culture, heritage, and identity.

Keywords: architectural culture and identity, climate change, forms from nature, Inuit architecture, locally sourced biodegradable materials, traditional architectural knowledge, traditional Inuit knowledge

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62 3D Interactions in Under Water Acoustic Simulationseffect of Green Synthesized Metal Nanoparticles on Gene Expression in an In-Vitro Model of Non-alcoholic Steatohepatitis

Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka

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Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.

Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity

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61 Development and Experimental Validation of Coupled Flow-Aerosol Microphysics Model for Hot Wire Generator

Authors: K. Ghosh, S. N. Tripathi, Manish Joshi, Y. S. Mayya, Arshad Khan, B. K. Sapra

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We have developed a CFD coupled aerosol microphysics model in the context of aerosol generation from a glowing wire. The governing equations can be solved implicitly for mass, momentum, energy transfer along with aerosol dynamics. The computationally efficient framework can simulate temporal behavior of total number concentration and number size distribution. This formulation uniquely couples standard K-Epsilon scheme with boundary layer model with detailed aerosol dynamics through residence time. This model uses measured temperatures (wire surface and axial/radial surroundings) and wire compositional data apart from other usual inputs for simulations. The model predictions show that bulk fluid motion and local heat distribution can significantly affect the aerosol behavior when the buoyancy effect in momentum transfer is considered. Buoyancy generated turbulence was found to be affecting parameters related to aerosol dynamics and transport as well. The model was validated by comparing simulated predictions with results obtained from six controlled experiments performed with a laboratory-made hot wire nanoparticle generator. Condensation particle counter (CPC) and scanning mobility particle sizer (SMPS) were used for measurement of total number concentration and number size distribution at the outlet of reactor cell during these experiments. Our model-predicted results were found to be in reasonable agreement with observed values. The developed model is fast (fully implicit) and numerically stable. It can be used specifically for applications in the context of the behavior of aerosol particles generated from glowing wire technique and in general for other similar large scale domains. Incorporation of CFD in aerosol microphysics framework provides a realistic platform to study natural convection driven systems/ applications. Aerosol dynamics sub-modules (nucleation, coagulation, wall deposition) have been coupled with Navier Stokes equations modified to include buoyancy coupled K-Epsilon turbulence model. Coupled flow-aerosol dynamics equation was solved numerically and in the implicit scheme. Wire composition and temperature (wire surface and cell domain) were obtained/measured, to be used as input for the model simulations. Model simulations showed a significant effect of fluid properties on the dynamics of aerosol particles. The role of buoyancy was highlighted by observation and interpretation of nucleation zones in the planes above the wire axis. The model was validated against measured temporal evolution, total number concentration and size distribution at the outlet of hot wire generator cell. Experimentally averaged and simulated total number concentrations were found to match closely, barring values at initial times. Steady-state number size distribution matched very well for sub 10 nm particle diameters while reasonable differences were noticed for higher size ranges. Although tuned specifically for the present context (i.e., aerosol generation from hotwire generator), the model can also be used for diverse applications, e.g., emission of particles from hot zones (chimneys, exhaust), fires and atmospheric cloud dynamics.

Keywords: nanoparticles, k-epsilon model, buoyancy, CFD, hot wire generator, aerosol dynamics

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60 Sensorless Machine Parameter-Free Control of Doubly Fed Reluctance Wind Turbine Generator

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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59 Long-Term Tillage, Lime Matter and Cover Crop Effects under Heavy Soil Conditions in Northern Lithuania

Authors: Aleksandras Velykis, Antanas Satkus

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Clay loam and clay soils are typical for northern Lithuania. These soils are susceptible to physical degradation in the case of intensive use of heavy machinery for field operations. However, clayey soils having poor physical properties by origin require more intensive tillage to maintain proper physical condition for grown crops. Therefore not only choice of suitable tillage system is very important for these soils in the region, but also additional search of other measures is essential for good soil physical state maintenance. Research objective: To evaluate the long-term effects of different intensity tillage as well as its combinations with supplementary agronomic practices on improvement of soil physical conditions and environmental sustainability. The experiment examined the influence of deep and shallow ploughing, ploughless tillage, combinations of ploughless tillage with incorporation of lime sludge and cover crop for green manure and application of the same cover crop for mulch without autumn tillage under spring and winter crop growing conditions on clay loam (27% clay, 50% silt, 23% sand) Endocalcaric Endogleyic Cambisol. Methods: The indicators characterizing the impact of investigated measures were determined using the following methods and devices: Soil dry bulk density – by Eijkelkamp cylinder (100 cm3), soil water content – by weighing, soil structure – by Retsch sieve shaker, aggregate stability – by Eijkelkamp wet sieving apparatus, soil mineral nitrogen – in 1 N KCL extract using colorimetric method. Results: Clay loam soil physical state (dry bulk density, structure, aggregate stability, water content) depends on tillage system and its combination with additional practices used. Application of cover crop winter mulch without tillage in autumn, ploughless tillage and shallow ploughing causes the compaction of bottom (15-25 cm) topsoil layer. However, due to ploughless tillage the soil dry bulk density in subsoil (25-35 cm) layer is less compared to deep ploughing. Soil structure in the upper (0-15 cm) topsoil layer and in the seedbed (0-5 cm), prepared for spring crops is usually worse when applying the ploughless tillage or cover crop mulch without autumn tillage. Application of lime sludge under ploughless tillage conditions helped to avoid the compaction and structure worsening in upper topsoil layer, as well as increase aggregate stability. Application of reduced tillage increased soil water content at upper topsoil layer directly after spring crop sowing. However, due to reduced tillage the water content in all topsoil markedly decreased when droughty periods lasted for a long time. Combination of reduced tillage with cover crop for green manure and winter mulch is significant for preserving the environment. Such application of cover crops reduces the leaching of mineral nitrogen into the deeper soil layers and environmental pollution. This work was supported by the National Science Program ‘The effect of long-term, different-intensity management of resources on the soils of different genesis and on other components of the agro-ecosystems’ [grant number SIT-9/2015] funded by the Research Council of Lithuania.

Keywords: clay loam, endocalcaric endogleyic cambisol, mineral nitrogen, physical state

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58 Made on Land, Ends Up in the Water "I-Clare" Intelligent Remediation System for Removal of Harmful Contaminants in Water using Modified Reticulated Vitreous Carbon Foam

Authors: Sabina Żołędowska, Tadeusz Ossowski, Robert Bogdanowicz, Jacek Ryl, Paweł Rostkowski, Michał Kruczkowski, Michał Sobaszek, Zofia Cebula, Grzegorz Skowierzak, Paweł Jakóbczyk, Lilit Hovhannisyan, Paweł Ślepski, Iwona Kaczmarczyk, Mattia Pierpaoli, Bartłomiej Dec, Dawid Nidzworski

Abstract:

The circular economy of water presents a pressing environmental challenge in our society. Water contains various harmful substances, such as drugs, antibiotics, hormones, and dioxides, which can pose silent threats. Water pollution has severe consequences for aquatic ecosystems. It disrupts the balance of ecosystems by harming aquatic plants, animals, and microorganisms. Water pollution poses significant risks to human health. Exposure to toxic chemicals through contaminated water can have long-term health effects, such as cancer, developmental disorders, and hormonal imbalances. However, effective remediation systems can be implemented to remove these contaminants using electrocatalytic processes, which offer an environmentally friendly alternative to other treatment methods, and one of them is the innovative iCLARE system. The project's primary focus revolves around a few main topics: Reactor design and construction, selection of a specific type of reticulated vitreous carbon foams (RVC), analytical studies of harmful contaminants parameters and AI implementation. This high-performance electrochemical reactor will be build based on a novel type of electrode material. The proposed approach utilizes the application of reticulated vitreous carbon foams (RVC) with deposited modified metal oxides (MMO) and diamond thin films. The following setup is characterized by high surface area development and satisfactory mechanical and electrochemical properties, designed for high electrocatalytic process efficiency. The consortium validated electrode modification methods that are the base of the iCLARE product and established the procedures for the detection of chemicals detection: - deposition of metal oxides WO3 and V2O5-deposition of boron-doped diamond/nanowalls structures by CVD process. The chosen electrodes (porous Ferroterm electrodes) were stress tested for various parameters that might occur inside the iCLARE machine–corosis, the long-term structure of the electrode surface during electrochemical processes, and energetic efficacy using cyclic polarization and electrochemical impedance spectroscopy (before and after electrolysis) and dynamic electrochemical impedance spectroscopy (DEIS). This tool allows real-time monitoring of the changes at the electrode/electrolyte interphase. On the other hand, the toxicity of iCLARE chemicals and products of electrolysis are evaluated before and after the treatment using MARA examination (IBMM) and HPLC-MS-MS (NILU), giving us information about the harmfulness of using electrode material and the efficiency of iClare system in the disposal of pollutants. Implementation of data into the system that uses artificial intelligence and the possibility of practical application is in progress (SensDx).

Keywords: waste water treatement, RVC, electrocatalysis, paracetamol

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

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

Abstract:

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

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

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56 Chronic Impact of Silver Nanoparticle on Aerobic Wastewater Biofilm

Authors: Sanaz Alizadeh, Yves Comeau, Arshath Abdul Rahim, Sunhasis Ghoshal

Abstract:

The application of silver nanoparticles (AgNPs) in personal care products, various household and industrial products has resulted in an inevitable environmental exposure of such engineered nanoparticles (ENPs). Ag ENPs, released via household and industrial wastes, reach water resource recovery facilities (WRRFs), yet the fate and transport of ENPs in WRRFs and their potential risk in the biological wastewater processes are poorly understood. Accordingly, our main objective was to elucidate the impact of long-term continuous exposure to AgNPs on biological activity of aerobic wastewater biofilm. The fate, transport and toxicity of 10 μg.L-1and 100 μg.L-1 PVP-stabilized AgNPs (50 nm) were evaluated in an attached growth biological treatment process, using lab-scale moving bed bioreactors (MBBRs). Two MBBR systems for organic matter removal were fed with a synthetic influent and operated at a hydraulic retention time (HRT) of 180 min and 60% volumetric filling ratio of Anox-K5 carriers with specific surface area of 800 m2/m3. Both reactors were operated for 85 days after reaching steady state conditions to develop a mature biofilm. The impact of AgNPs on the biological performance of the MBBRs was characterized over a period of 64 days in terms of the filtered biodegradable COD (SCOD) removal efficiency, the biofilm viability and key enzymatic activities (α-glucosidase and protease). The AgNPs were quantitatively characterized using single-particle inductively coupled plasma mass spectroscopy (spICP-MS), determining simultaneously the particle size distribution, particle concentration and dissolved silver content in influent, bioreactor and effluent samples. The generation of reactive oxygen species and the oxidative stress were assessed as the proposed toxicity mechanism of AgNPs. Results indicated that a low concentration of AgNPs (10 μg.L-1) did not significantly affect the SCOD removal efficiency whereas a significant reduction in treatment efficiency (37%) was observed at 100 μg.L-1AgNPs. Neither the viability nor the enzymatic activities of biofilm were affected at 10 μg.L-1AgNPs but a higher concentration of AgNPs induced cell membrane integrity damage resulting in 31% loss of viability and reduced α-glucosidase and protease enzymatic activities by 31% and 29%, respectively, over the 64-day exposure period. The elevated intercellular ROS in biofilm at a higher AgNPs concentration over time was consistent with a reduced biological biofilm performance, confirming the occurrence of a nanoparticle-induced oxidative stress in the heterotrophic biofilm. The spICP-MS analysis demonstrated a decrease in the nanoparticles concentration over the first 25 days, indicating a significant partitioning of AgNPs into the biofilm matrix in both reactors. The concentration of nanoparticles increased in effluent of both reactors after 25 days, however, indicating a decreased retention capacity of AgNPs in biofilm. The observed significant detachment of biofilm also contributed to a higher release of nanoparticles due to cell-wall destabilizing properties of AgNPs as an antimicrobial agent. The removal efficiency of PVP-AgNPs and the biofilm biological responses were a function of nanoparticle concentration and exposure time. This study contributes to a better understanding of the fate and behavior of AgNPs in biological wastewater processes, providing key information that can be used to predict the environmental risks of ENPs in aquatic ecosystems.

Keywords: biofilm, silver nanoparticle, single particle ICP-MS, toxicity, wastewater

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55 The Ductile Fracture of Armor Steel Targets Subjected to Ballistic Impact and Perforation: Calibration of Four Damage Criteria

Authors: Imen Asma Mbarek, Alexis Rusinek, Etienne Petit, Guy Sutter, Gautier List

Abstract:

Over the past two decades, the automotive, aerospace and army industries have been paying an increasing attention to Finite Elements (FE) numerical simulations of the fracture process of their structures. Thanks to the numerical simulations, it is nowadays possible to analyze several problems involving costly and dangerous extreme loadings safely and at a reduced cost such as blast or ballistic impact problems. The present paper is concerned with ballistic impact and perforation problems involving ductile fracture of thin armor steel targets. The target fracture process depends usually on various parameters: the projectile nose shape, the target thickness and its mechanical properties as well as the impact conditions (friction, oblique/normal impact...). In this work, the investigations are concerned with the normal impact of a conical head-shaped projectile on thin armor steel targets. The main aim is to establish a comparative study of four fracture criteria that are commonly used in the fracture process simulations of structures subjected to extreme loadings such as ballistic impact and perforation. Usually, the damage initiation results from a complex physical process that occurs at the micromechanical scale. On a macro scale and according to the following fracture models, the variables on which the fracture depends are mainly the stress triaxiality ƞ, the strain rate, temperature T, and eventually the Lode angle parameter Ɵ. The four failure criteria are: the critical strain to failure model, the Johnson-Cook model, the Wierzbicki model and the Modified Hosford-Coulomb model MHC. Using the SEM, the observations of the fracture facies of tension specimen and of armor steel targets impacted at low and high incident velocities show that the fracture of the specimens is a ductile fracture. The failure mode of the targets is petalling with crack propagation and the fracture facies are covered with micro-cavities. The parameters of each ductile fracture model have been identified for three armor steels and the applicability of each criterion was evaluated using experimental investigations coupled to numerical simulations. Two loading paths were investigated in this study, under a wide range of strain rates. Namely, quasi-static and intermediate uniaxial tension and quasi-static and dynamic double shear testing allow covering various values of stress triaxiality ƞ and of the Lode angle parameter Ɵ. All experiments were conducted on three different armor steel specimen under quasi-static strain rates ranging from 10-4 to 10-1 1/s and at three different temperatures ranging from 297K to 500K, allowing drawing the influence of temperature on the fracture process. Intermediate tension testing was coupled to dynamic double shear experiments conducted on the Hopkinson tube device, allowing to spot the effect of high strain rate on the damage evolution and the crack propagation. The aforementioned fracture criteria are implemented into the FE code ABAQUS via VUMAT subroutine and they were coupled to suitable constitutive relations allow having reliable results of ballistic impact problems simulation. The calibration of the four damage criteria as well as a concise evaluation of the applicability of each criterion are detailed in this work.

Keywords: armor steels, ballistic impact, damage criteria, ductile fracture, SEM

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54 A Microwave Heating Model for Endothermic Reaction in the Cement Industry

Authors: Sofia N. Gonçalves, Duarte M. S. Albuquerque, José C. F. Pereira

Abstract:

Microwave technology has been gaining importance in contributing to decarbonization processes in high energy demand industries. Despite the several numerical models presented in the literature, a proper Verification and Validation exercise is still lacking. This is important and required to evaluate the physical process model accuracy and adequacy. Another issue addresses impedance matching, which is an important mechanism used in microwave experiments to increase electromagnetic efficiency. Such mechanism is not available in current computational tools, thus requiring an external numerical procedure. A numerical model was implemented to study the continuous processing of limestone with microwave heating. This process requires the material to be heated until a certain temperature that will prompt a highly endothermic reaction. Both a 2D and 3D model were built in COMSOL Multiphysics to solve the two-way coupling between Maxwell and Energy equations, along with the coupling between both heat transfer phenomena and limestone endothermic reaction. The 2D model was used to study and evaluate the required numerical procedure, being also a benchmark test, allowing other authors to implement impedance matching procedures. To achieve this goal, a controller built in MATLAB was used to continuously matching the cavity impedance and predicting the required energy for the system, thus successfully avoiding energy inefficiencies. The 3D model reproduces realistic results and therefore supports the main conclusions of this work. Limestone was modeled as a continuous flow under the transport of concentrated species, whose material and kinetics properties were taken from literature. Verification and Validation of the coupled model was taken separately from the chemical kinetic model. The chemical kinetic model was found to correctly describe the chosen kinetic equation by comparing numerical results with experimental data. A solution verification was made for the electromagnetic interface, where second order and fourth order accurate schemes were found for linear and quadratic elements, respectively, with numerical uncertainty lower than 0.03%. Regarding the coupled model, it was demonstrated that the numerical error would diverge for the heat transfer interface with the mapped mesh. Results showed numerical stability for the triangular mesh, and the numerical uncertainty was less than 0.1%. This study evaluated limestone velocity, heat transfer, and load influence on thermal decomposition and overall process efficiency. The velocity and heat transfer coefficient were studied with the 2D model, while different loads of material were studied with the 3D model. Both models demonstrated to be highly unstable when solving non-linear temperature distributions. High velocity flows exhibited propensity to thermal runways, and the thermal efficiency showed the tendency to stabilize for the higher velocities and higher filling ratio. Microwave efficiency denoted an optimal velocity for each heat transfer coefficient, pointing out that electromagnetic efficiency is a consequence of energy distribution uniformity. The 3D results indicated the inefficient development of the electric field for low filling ratios. Thermal efficiencies higher than 90% were found for the higher loads and microwave efficiencies up to 75% were accomplished. The 80% fill ratio was demonstrated to be the optimal load with an associated global efficiency of 70%.

Keywords: multiphysics modeling, microwave heating, verification and validation, endothermic reactions modeling, impedance matching, limestone continuous processing

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53 A Multimodal Discourse Analysis of Gender Representation on Health and Fitness Magazine Cover Pages

Authors: Nashwa Elyamany

Abstract:

In visual cultures, namely that of the United States, media representations are such influential and pervasive reflections of societal norms and expectations to the extent that they impact the manner in which both genders view themselves. Health and fitness magazines fall within the realm of visual culture. Since the main goal of communication is to ensure proper dissemination of information in order for the target audience to grasp the intended messages, it becomes imperative that magazine publishers, editors, advertisers and image producers use different modes of communication within their reach to convey messages to their readers and viewers. A rapid waxing flow of multimodality floods popular discourse, particularly health and fitness magazine cover pages. The use of well-crafted cover lines and visual images is imbued with agendas, consumerist ideologies and properties capable of effectively conveying implicit and explicit meaning to potential readers and viewers. In essence, the primary goal of this thesis is to interrogate the multi-semiotic operations and manifestations of hegemonic masculinity and femininity in male and female body culture, particularly on the cover pages of the twin American magazines Men's Health and Women's Health using corpora that spanned from 2011 to the mid of 2016. The researcher explores the semiotic resources that contribute to shaping and legitimizing a new form of postmodern, consumerist, gendered discourse that positions the reader-viewer ideologically. Methodologically, the researcher carries out analysis on the macro and micro levels. On the macro level, the researcher takes on a critical stance to illuminate the ideological nature of the multimodal ensemble of the cover pages, and, on the micro level, seeks to put forward new theoretical and methodological routes through which the semiotic choices well invested on the media texts can be more objectively scrutinized. On the macro level, a 'themes' analysis is initially conducted to isolate the overarching themes that dominate the fitness discourse on the cover pages under study. It is argued that variation in terms of frequencies of such themes is indicative, broadly speaking, of which facets of hegemonic masculinity and femininity are infused in the fitness discourse on the cover pages. On the micro level, this research work encompasses three sub-levels of analysis. The researcher follows an SF-MMDA approach, drawing on a trio of analytical frameworks: Halliday's SFG for the verbal analysis; Kress & van Leeuween's VG for the visual analysis; and CMT in relation to Sperber & Wilson's RT for the pragma-cognitive analysis of multimodal metaphors and metonymies. The data is presented in terms of detailed descriptions in conjunction with frequency tables, ANOVA with alpha=0.05 and MANOVA in the multiple phases of analysis. Insights and findings from this multi-faceted, social-semiotic analysis are interpreted in light of Cultivation Theory, Self-objectification Theory and the literature to date. Implications for future research include the implementation of a multi-dimensional approach whereby linguistic and visual analytical models are deployed with special regards to cultural variation.

Keywords: gender, hegemony, magazine cover page, multimodal discourse analysis, multimodal metaphor, multimodal metonymy, systemic functional grammar, visual grammar

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52 Experimental Characterisation of Composite Panels for Railway Flooring

Authors: F. Pedro, S. Dias, A. Tadeu, J. António, Ó. López, A. Coelho

Abstract:

Railway transportation is considered the most economical and sustainable way to travel. However, future mobility brings important challenges to railway operators. The main target is to develop solutions that stimulate sustainable mobility. The research and innovation goals for this domain are efficient solutions, ensuring an increased level of safety and reliability, improved resource efficiency, high availability of the means (train), and satisfied passengers with the travel comfort level. These requirements are in line with the European Strategic Agenda for the 2020 rail sector, promoted by the European Rail Research Advisory Council (ERRAC). All these aspects involve redesigning current equipment and, in particular, the interior of the carriages. Recent studies have shown that two of the most important requirements for passengers are reasonable ticket prices and comfortable interiors. Passengers tend to use their travel time to rest or to work, so train interiors and their systems need to incorporate features that meet these requirements. Among the various systems that integrate train interiors, the flooring system is one of the systems with the greatest impact on passenger safety and comfort. It is also one of the systems that takes more time to install on the train, and which contributes seriously to the weight (mass) of all interior systems. Additionally, it presents a strong impact on manufacturing costs. The design of railway floor, in the development phase, is usually made relying on a design software that allows to draw and calculate several solutions in a short period of time. After obtaining the best solution, considering the goals previously defined, experimental data is always necessary and required. This experimental phase has such great significance, that its outcome can provoke the revision of the designed solution. This paper presents the methodology and some of the results of an experimental characterisation of composite panels for railway application. The mechanical tests were made for unaged specimens and for specimens that suffered some type of aging, i.e. heat, cold and humidity cycles or freezing/thawing cycles. These conditionings aim to simulate not only the time effect, but also the impact of severe environmental conditions. Both full solutions and separated components/materials were tested. For the full solution, (panel) these were: four-point bending tests, tensile shear strength, tensile strength perpendicular to the plane, determination of the spreading of water, and impact tests. For individual characterisation of the components, more specifically for the covering, the following tests were made: determination of the tensile stress-strain properties, determination of flexibility, determination of tear strength, peel test, tensile shear strength test, adhesion resistance test and dimensional stability. The main conclusions were that experimental characterisation brings a huge contribution to understand the behaviour of the materials both individually and assembled. This knowledge contributes to the increase the quality and improvements of premium solutions. This research work was framed within the POCI-01-0247-FEDER-003474 (coMMUTe) Project funded by Portugal 2020 through the COMPETE 2020.

Keywords: durability, experimental characterization, mechanical tests, railway flooring system

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51 Neologisms and Word-Formation Processes in Board Game Rulebook Corpus: Preliminary Results

Authors: Athanasios Karasimos, Vasiliki Makri

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This research focuses on the design and development of the first text Corpus based on Board Game Rulebooks (BGRC) with direct application on the morphological analysis of neologisms and tendencies in word-formation processes. Corpus linguistics is a dynamic field that examines language through the lens of vast collections of texts. These corpora consist of diverse written and spoken materials, ranging from literature and newspapers to transcripts of everyday conversations. By morphologically analyzing these extensive datasets, morphologists can gain valuable insights into how language functions and evolves, as these extensive datasets can reflect the byproducts of inflection, derivation, blending, clipping, compounding, and neology. This entails scrutinizing how words are created, modified, and combined to convey meaning in a corpus of challenging, creative, and straightforward texts that include rules, examples, tutorials, and tips. Board games teach players how to strategize, consider alternatives, and think flexibly, which are critical elements in language learning. Their rulebooks reflect not only their weight (complexity) but also the language properties of each genre and subgenre of these games. Board games are a captivating realm where strategy, competition, and creativity converge. Beyond the excitement of gameplay, board games also spark the art of word creation. Word games, like Scrabble, Codenames, Bananagrams, Wordcraft, Alice in the Wordland, Once uUpona Time, challenge players to construct words from a pool of letters, thus encouraging linguistic ingenuity and vocabulary expansion. These games foster a love for language, motivating players to unearth obscure words and devise clever combinations. On the other hand, the designers and creators produce rulebooks, where they include their joy of discovering the hidden potential of language, igniting the imagination, and playing with the beauty of words, making these games a delightful fusion of linguistic exploration and leisurely amusement. In this research, more than 150 rulebooks in English from all types of modern board games, either language-independent or language-dependent, are used to create the BGRC. A representative sample of each genre (family, party, worker placement, deckbuilding, dice, and chance games, strategy, eurogames, thematic, role-playing, among others) was selected based on the score from BoardGameGeek, the size of the texts and the level of complexity (weight) of the game. A morphological model with morphological networks, multi-word expressions, and word-creation mechanics based on the complexity of the textual structure, difficulty, and board game category will be presented. In enabling the identification of patterns, trends, and variations in word formation and other morphological processes, this research aspires to make avail of this creative yet strict text genre so as to (a) give invaluable insight into morphological creativity and innovation that (re)shape the lexicon of the English language and (b) test morphological theories. Overall, it is shown that corpus linguistics empowers us to explore the intricate tapestry of language, and morphology in particular, revealing its richness, flexibility, and adaptability in the ever-evolving landscape of human expression.

Keywords: board game rulebooks, corpus design, morphological innovations, neologisms, word-formation processes

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50 Hybrid Materials on the Basis of Magnetite and Magnetite-Gold Nanoparticles for Biomedical Application

Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

Abstract:

During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

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49 Enhancing Scalability in Ethereum Network Analysis: Methods and Techniques

Authors: Stefan K. Behfar

Abstract:

The rapid growth of the Ethereum network has brought forth the urgent need for scalable analysis methods to handle the increasing volume of blockchain data. In this research, we propose efficient methodologies for making Ethereum network analysis scalable. Our approach leverages a combination of graph-based data representation, probabilistic sampling, and parallel processing techniques to achieve unprecedented scalability while preserving critical network insights. Data Representation: We develop a graph-based data representation that captures the underlying structure of the Ethereum network. Each block transaction is represented as a node in the graph, while the edges signify temporal relationships. This representation ensures efficient querying and traversal of the blockchain data. Probabilistic Sampling: To cope with the vastness of the Ethereum blockchain, we introduce a probabilistic sampling technique. This method strategically selects a representative subset of transactions and blocks, allowing for concise yet statistically significant analysis. The sampling approach maintains the integrity of the network properties while significantly reducing the computational burden. Graph Convolutional Networks (GCNs): We incorporate GCNs to process the graph-based data representation efficiently. The GCN architecture enables the extraction of complex spatial and temporal patterns from the sampled data. This combination of graph representation and GCNs facilitates parallel processing and scalable analysis. Distributed Computing: To further enhance scalability, we adopt distributed computing frameworks such as Apache Hadoop and Apache Spark. By distributing computation across multiple nodes, we achieve a significant reduction in processing time and enhanced memory utilization. Our methodology harnesses the power of parallelism, making it well-suited for large-scale Ethereum network analysis. Evaluation and Results: We extensively evaluate our methodology on real-world Ethereum datasets covering diverse time periods and transaction volumes. The results demonstrate its superior scalability, outperforming traditional analysis methods. Our approach successfully handles the ever-growing Ethereum data, empowering researchers and developers with actionable insights from the blockchain. Case Studies: We apply our methodology to real-world Ethereum use cases, including detecting transaction patterns, analyzing smart contract interactions, and predicting network congestion. The results showcase the accuracy and efficiency of our approach, emphasizing its practical applicability in real-world scenarios. Security and Robustness: To ensure the reliability of our methodology, we conduct thorough security and robustness evaluations. Our approach demonstrates high resilience against adversarial attacks and perturbations, reaffirming its suitability for security-critical blockchain applications. Conclusion: By integrating graph-based data representation, GCNs, probabilistic sampling, and distributed computing, we achieve network scalability without compromising analytical precision. This approach addresses the pressing challenges posed by the expanding Ethereum network, opening new avenues for research and enabling real-time insights into decentralized ecosystems. Our work contributes to the development of scalable blockchain analytics, laying the foundation for sustainable growth and advancement in the domain of blockchain research and application.

Keywords: Ethereum, scalable network, GCN, probabilistic sampling, distributed computing

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

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

Abstract:

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

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

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47 Effect of Preoxidation on the Effectiveness of Gd₂O₃ Nanoparticles Applied as a Source of Active Element in the Crofer 22 APU Coated with a Protective-conducting Spinel Layer

Authors: Łukasz Mazur, Kamil Domaradzki, Maciej Bik, Tomasz Brylewski, Aleksander Gil

Abstract:

Interconnects used in solid oxide fuel and electrolyzer cells (SOFCₛ/SOECs) serve several important functions, and therefore interconnect materials must exhibit certain properties. Their thermal expansion coefficient needs to match that of the ceramic components of these devices – the electrolyte, anode and cathode. Interconnects also provide structural rigidity to the entire device, which is why interconnect materials must exhibit sufficient mechanical strength at high temperatures. Gas-tightness is also a prerequisite since they separate gas reagents, and they also must provide very good electrical contact between neighboring cells over the entire operating time. High-chromium ferritic steels meets these requirements to a high degree but are affected by the formation of a Cr₂O₃ scale, which leads to increased electrical resistance. The final criterion for interconnect materials is chemical inertness in relation to the remaining cell components. In the case of ferritic steels, this has proved difficult due to the formation of volatile and reactive oxyhydroxides observed when Cr₂O3 is exposed to oxygen and water vapor. This process is particularly harmful on the cathode side in SOFCs and the anode side in SOECs. To mitigate this, protective-conducting ceramic coatings can be deposited on an interconnect's surface. The area-specific resistance (ASR) of a single interconnect cannot exceed 0.1 m-2 at any point of the device's operation. The rate at which the CrO₃ scale grows on ferritic steels can be reduced significantly via the so-called reactive element effect (REE). Research has shown that the deposition of Gd₂O₃ nanoparticles on the surface of the Crofer 22 APU, already modified using a protective-conducting spinel layer, further improves the oxidation resistance of this steel. However, the deposition of the manganese-cobalt spinel layer is a rather complex process and is performed at high temperatures in reducing and oxidizing atmospheres. There was thus reason to believe that this process may reduce the effectiveness of Gd₂O₃ nanoparticles added as an active element source. The objective of the present study was, therefore, to determine any potential impact by introducing a preoxidation stage after the nanoparticle deposition and before the steel is coated with the spinel. This should have allowed the nanoparticles to incorporate into the interior of the scale formed on the steel. Different samples were oxidized for 7000 h in air at 1073 K under quasi-isothermal conditions. The phase composition, chemical composition, and microstructure of the oxidation products formed on the samples were determined using X-ray diffraction, Raman spectroscopy, and scanning electron microscopy combined with energy-dispersive X-ray spectroscopy. A four-point, two-probe DC method was applied to measure ASR. It was found that coating deposition does indeed reduce the beneficial effect of Gd₂O₃ addition, since the smallest mass gain and the lowest ASR value were determined for the sample for which the additional preoxidation stage had been performed. It can be assumed that during this stage, gadolinium incorporates into and segregates at grain boundaries in the thin Cr₂O₃ that is forming. This allows the Gd₂O₃ nanoparticles to be a more effective source of the active element.

Keywords: interconnects, oxide nanoparticles, reactive element effect, SOEC, SOFC

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46 Quasi-Photon Monte Carlo on Radiative Heat Transfer: An Importance Sampling and Learning Approach

Authors: Utkarsh A. Mishra, Ankit Bansal

Abstract:

At high temperature, radiative heat transfer is the dominant mode of heat transfer. It is governed by various phenomena such as photon emission, absorption, and scattering. The solution of the governing integrodifferential equation of radiative transfer is a complex process, more when the effect of participating medium and wavelength properties are taken into consideration. Although a generic formulation of such radiative transport problem can be modeled for a wide variety of problems with non-gray, non-diffusive surfaces, there is always a trade-off between simplicity and accuracy of the problem. Recently, solutions of complicated mathematical problems with statistical methods based on randomization of naturally occurring phenomena have gained significant importance. Photon bundles with discrete energy can be replicated with random numbers describing the emission, absorption, and scattering processes. Photon Monte Carlo (PMC) is a simple, yet powerful technique, to solve radiative transfer problems in complicated geometries with arbitrary participating medium. The method, on the one hand, increases the accuracy of estimation, and on the other hand, increases the computational cost. The participating media -generally a gas, such as CO₂, CO, and H₂O- present complex emission and absorption spectra. To model the emission/absorption accurately with random numbers requires a weighted sampling as different sections of the spectrum carries different importance. Importance sampling (IS) was implemented to sample random photon of arbitrary wavelength, and the sampled data provided unbiased training of MC estimators for better results. A better replacement to uniform random numbers is using deterministic, quasi-random sequences. Halton, Sobol, and Faure Low-Discrepancy Sequences are used in this study. They possess better space-filling performance than the uniform random number generator and gives rise to a low variance, stable Quasi-Monte Carlo (QMC) estimators with faster convergence. An optimal supervised learning scheme was further considered to reduce the computation costs of the PMC simulation. A one-dimensional plane-parallel slab problem with participating media was formulated. The history of some randomly sampled photon bundles is recorded to train an Artificial Neural Network (ANN), back-propagation model. The flux was calculated using the standard quasi PMC and was considered to be the training target. Results obtained with the proposed model for the one-dimensional problem are compared with the exact analytical and PMC model with the Line by Line (LBL) spectral model. The approximate variance obtained was around 3.14%. Results were analyzed with respect to time and the total flux in both cases. A significant reduction in variance as well a faster rate of convergence was observed in the case of the QMC method over the standard PMC method. However, the results obtained with the ANN method resulted in greater variance (around 25-28%) as compared to the other cases. There is a great scope of machine learning models to help in further reduction of computation cost once trained successfully. Multiple ways of selecting the input data as well as various architectures will be tried such that the concerned environment can be fully addressed to the ANN model. Better results can be achieved in this unexplored domain.

Keywords: radiative heat transfer, Monte Carlo Method, pseudo-random numbers, low discrepancy sequences, artificial neural networks

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45 Enabling Wire Arc Additive Manufacturing in Aircraft Landing Gear Production and Its Benefits

Authors: Jun Wang, Chenglei Diao, Emanuele Pagone, Jialuo Ding, Stewart Williams

Abstract:

As a crucial component in aircraft, landing gear systems are responsible for supporting the plane during parking, taxiing, takeoff, and landing. Given the need for high load-bearing capacity over extended periods, 300M ultra-high strength steel (UHSS) is often the material of choice for crafting these systems due to its exceptional strength, toughness, and fatigue resistance. In the quest for cost-effective and sustainable manufacturing solutions, Wire Arc Additive Manufacturing (WAAM) emerges as a promising alternative for fabricating 300M UHSS landing gears. This is due to its advantages in near-net-shape forming of large components, cost-efficiency, and reduced lead times. Cranfield University has conducted an extensive preliminary study on WAAM 300M UHSS, covering feature deposition, interface analysis, and post-heat treatment. Both Gas Metal Arc (GMA) and Plasma Transferred Arc (PTA)-based WAAM methods were explored, revealing their feasibility for defect-free manufacturing. However, as-deposited 300M features showed lower strength but higher ductility compared to their forged counterparts. Subsequent post-heat treatments were effective in normalising the microstructure and mechanical properties, meeting qualification standards. A 300M UHSS landing gear demonstrator was successfully created using PTA-based WAAM, showcasing the method's precision and cost-effectiveness. The demonstrator, measuring Ф200mm x 700mm, was completed in 16 hours, using 7 kg of material at a deposition rate of 1.3kg/hr. This resulted in a significant reduction in the Buy-to-Fly (BTF) ratio compared to traditional manufacturing methods, further validating WAAM's potential for this application. A "cradle-to-gate" environmental impact assessment, which considers the cumulative effects from raw material extraction to customer shipment, has revealed promising outcomes. Utilising Wire Arc Additive Manufacturing (WAAM) for landing gear components significantly reduces the need for raw material extraction and refinement compared to traditional subtractive methods. This, in turn, lessens the burden on subsequent manufacturing processes, including heat treatment, machining, and transportation. Our estimates indicate that the carbon footprint of the component could be halved when switching from traditional machining to WAAM. Similar reductions are observed in embodied energy consumption and other environmental impact indicators, such as emissions to air, water, and land. Additionally, WAAM offers the unique advantage of part repair by redepositing only the necessary material, a capability not available through conventional methods. Our research shows that WAAM-based repairs can drastically reduce environmental impact, even when accounting for additional transportation for repairs. Consequently, WAAM emerges as a pivotal technology for reducing environmental impact in manufacturing, aiding the industry in its crucial and ambitious journey towards Net Zero. This study paves the way for transformative benefits across the aerospace industry, as we integrate manufacturing into a hybrid solution that offers substantial savings and access to more sustainable technologies for critical component production.

Keywords: WAAM, aircraft landing gear, microstructure, mechanical performance, life cycle assessment

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44 Production of Insulin Analogue SCI-57 by Transient Expression in Nicotiana benthamiana

Authors: Adriana Muñoz-Talavera, Ana Rosa Rincón-Sánchez, Abraham Escobedo-Moratilla, María Cristina Islas-Carbajal, Miguel Ángel Gómez-Lim

Abstract:

The highest rates of diabetes incidence and prevalence worldwide will increase the number of diabetic patients requiring insulin or insulin analogues. Then, current production systems would not be sufficient to meet the future market demands. Therefore, developing efficient expression systems for insulin and insulin analogues are needed. In addition, insulin analogues with better pharmacokinetics and pharmacodynamics properties and without mitogenic potential will be required. SCI-57 (single chain insulin-57) is an insulin analogue having 10 times greater affinity to the insulin receptor, higher resistance to thermal degradation than insulin, native mitogenicity and biological effect. Plants as expression platforms have been used to produce recombinant proteins because of their advantages such as cost-effectiveness, posttranslational modifications, absence of human pathogens and high quality. Immunoglobulin production with a yield of 50% has been achieved by transient expression in Nicotiana benthamiana (Nb). The aim of this study is to produce SCI-57 by transient expression in Nb. Methodology: DNA sequence encoding SCI-57 was cloned in pICH31070. This construction was introduced into Agrobacterium tumefaciens by electroporation. The resulting strain was used to infiltrate leaves of Nb. In order to isolate SCI-57, leaves from transformed plants were incubated 3 hours with the extraction buffer therefore filtrated to remove solid material. The resultant protein solution was subjected to anion exchange chromatography on an FPLC system and ultrafiltration to purify SCI-57. Detection of SCI-57 was made by electrophoresis pattern (SDS-PAGE). Protein band was digested with trypsin and the peptides were analyzed by Liquid chromatography tandem-mass spectrometry (LC-MS/MS). A purified protein sample (20µM) was analyzed by ESI-Q-TOF-MS to obtain the ionization pattern and the exact molecular weight determination. Chromatography pattern and impurities detection were performed using RP-HPLC using recombinant insulin as standard. The identity of the SCI-57 was confirmed by anti-insulin ELISA. The total soluble protein concentration was quantified by Bradford assay. Results: The expression cassette was verified by restriction mapping (5393 bp fragment). The SDS-PAGE of crude leaf extract (CLE) of transformed plants, revealed a protein of about 6.4 kDa, non-present in CLE of untransformed plants. The LC-MS/MS results displayed one peptide with a high score that matches SCI-57 amino acid sequence in the sample, confirming the identity of SCI-57. From the purified SCI-57 sample (PSCI-57) the most intense charge state was 1069 m/z (+6) on the displayed ionization pattern corresponding to the molecular weight of SCI-57 (6412.6554 Da). The RP-HPLC of the PSCI-57 shows the presence of a peak with similar retention time (rt) and UV spectroscopic profile to the insulin standard (SCI-57 rt=12.96 and insulin rt=12.70 min). The collected SCI-57 peak had ELISA signal. The total protein amount in CLE from transformed plants was higher compared to untransformed plants. Conclusions: Our results suggest the feasibility to produce insulin analogue SCI-57 by transient expression in Nicotiana benthamiana. Further work is being undertaken to evaluate the biological activity by glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes.

Keywords: insulin analogue, mass spectrometry, Nicotiana benthamiana, transient expression

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43 Railway Composite Flooring Design: Numerical Simulation and Experimental Studies

Authors: O. Lopez, F. Pedro, A. Tadeu, J. Antonio, A. Coelho

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The future of the railway industry lies in the innovation of lighter, more efficient and more sustainable trains. Weight optimizations in railway vehicles allow reducing power consumption and CO₂ emissions, increasing the efficiency of the engines and the maximum speed reached. Additionally, they reduce wear of wheels and rails, increase the space available for passengers, etc. Among the various systems that integrate railway interiors, the flooring system is one which has greater impact both on passenger safety and comfort, as well as on the weight of the interior systems. Due to the high weight saving potential, relative high mechanical resistance, good acoustic and thermal performance, ease of modular design, cost-effectiveness and long life, the use of new sustainable composite materials and panels provide the latest innovations for competitive solutions in the development of flooring systems. However, one of the main drawbacks of the flooring systems is their relatively poor resistance to point loads. Point loads in railway interiors can be caused by passengers or by components fixed to the flooring system, such as seats and restraint systems, handrails, etc. In this way, they can originate higher fatigue solicitations under service loads or zones with high stress concentrations under exceptional loads (higher longitudinal, transverse and vertical accelerations), thus reducing its useful life. Therefore, to verify all the mechanical and functional requirements of the flooring systems, many physical prototypes would be created during the design phase, with all of the high costs associated with it. Nowadays, the use of virtual prototyping methods by computer-aided design (CAD) and computer-aided engineering (CAE) softwares allow validating a product before committing to making physical test prototypes. The scope of this work was to current computer tools and integrate the processes of innovation, development, and manufacturing to reduce the time from design to finished product and optimise the development of the product for higher levels of performance and reliability. In this case, the mechanical response of several sandwich panels with different cores, polystyrene foams, and composite corks, were assessed, to optimise the weight and the mechanical performance of a flooring solution for railways. Sandwich panels with aluminum face sheets were tested to characterise its mechanical performance and determine the polystyrene foam and cork properties when used as inner cores. Then, a railway flooring solution was fully modelled (including the elastomer pads to provide the required vibration isolation from the car body) and perform structural simulations using FEM analysis to comply all the technical product specifications for the supply of a flooring system. Zones with high stress concentrations are studied and tested. The influence of vibration modes on the comfort level and stability is discussed. The information obtained with the computer tools was then completed with several mechanical tests performed on some solutions, and on specific components. The results of the numerical simulations and experimental campaign carried out are presented in this paper. This research work was performed as part of the POCI-01-0247-FEDER-003474 (coMMUTe) Project funded by Portugal 2020 through COMPETE 2020.

Keywords: cork agglomerate core, mechanical performance, numerical simulation, railway flooring system

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42 Production, Characterisation, and in vitro Degradation and Biocompatibility of a Solvent-Free Polylactic-Acid/Hydroxyapatite Composite for 3D-Printed Maxillofacial Bone-Regeneration Implants

Authors: Carlos Amnael Orozco-Diaz, Robert David Moorehead, Gwendolen Reilly, Fiona Gilchrist, Cheryl Ann Miller

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The current gold-standard for maxillofacial reconstruction surgery (MRS) utilizes auto-grafted cancellous bone as a filler. This study was aimed towards developing a polylactic-acid/hydroxyapatite (PLA-HA) composite suitable for fused-deposition 3D printing. Functionalization of the polymer through the addition of HA was directed to promoting bone-regeneration properties so that the material can rival the performance of cancellous bone grafts in terms of bone-lesion repair. This kind of composite enables the production of MRS implants based off 3D-reconstructions from image studies – namely computed tomography – for anatomically-correct fitting. The present study encompassed in-vitro degradation and in-vitro biocompatibility profiling for 3D-printed PLA and PLA-HA composites. PLA filament (Verbatim Co.) and Captal S hydroxyapatite micro-scale HA powder (Plasma Biotal Ltd) were used to produce PLA-HA composites at 5, 10, and 20%-by-weight HA concentration. These were extruded into 3D-printing filament, and processed in a BFB-3000 3D-Printer (3D Systems Co.) into tensile specimens, and were mechanically challenged as per ASTM D638-03. Furthermore, tensile specimens were subjected to accelerated degradation in phosphate-buffered saline solution at 70°C for 23 days, as per ISO-10993-13-2010. This included monitoring of mass loss (through dry-weighing), crystallinity (through thermogravimetric analysis/differential thermal analysis), molecular weight (through gel-permeation chromatography), and tensile strength. In-vitro biocompatibility analysis included cell-viability and extracellular matrix deposition, which were performed both on flat surfaces and on 3D-constructs – both produced through 3D-printing. Discs of 1 cm in diameter and cubic 3D-meshes of 1 cm3 were 3D printed in PLA and PLA-HA composites (n = 6). The samples were seeded with 5000 MG-63 osteosarcoma-like cells, with cell viability extrapolated throughout 21 days via resazurin reduction assays. As evidence of osteogenicity, collagen and calcium deposition were indirectly estimated through Sirius Red staining and Alizarin Red staining respectively. Results have shown that 3D printed PLA loses structural integrity as early as the first day of accelerated degradation, which was significantly faster than the literature suggests. This was reflected in the loss of tensile strength down to untestable brittleness. During degradation, mass loss, molecular weight, and crystallinity behaved similarly to results found in similar studies for PLA. All composite versions and pure PLA were found to perform equivalent to tissue-culture plastic (TCP) in supporting the seeded-cell population. Significant differences (p = 0.05) were found on collagen deposition for higher HA concentrations, with composite samples performing better than pure PLA and TCP. Additionally, per-cell-calcium deposition on the 3D-meshes was significantly lower when comparing 3D-meshes to discs of the same material (p = 0.05). These results support the idea that 3D-printable PLA-HA composites are a viable resorbable material for artificial grafts for bone-regeneration. Degradation data suggests that 3D-printing of these materials – as opposed to other manufacturing methods – might result in faster resorption than currently-used PLA implants.

Keywords: bone regeneration implants, 3D-printing, in vitro testing, biocompatibility, polymer degradation, polymer-ceramic composites

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41 Comparative Characteristics of Bacteriocins from Endemic Lactic Acid Bacteria

Authors: K. Karapetyan, F. Tkhruni, A. Aghajanyan, T. S. Balabekyan, L. Arstamyan

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Introduction: Globalization of the food supply has created the conditions favorable for the emergence and spread of food-borne and especially dangerous pathogens (EDP) in developing countries. The fresh-cut fruit and vegetable industry is searching for alternatives to replace chemical treatments with biopreservative approaches that ensure the safety of the processed foods product. Antimicrobial compounds of lactic acid bacteria (LAB) possess bactericidal or bacteriostatic activity against intestinal pathogens, spoilage organisms and food-borne pathogens such as Listeria monocytogenes, Staphylococcus aureus and Salmonella. Endemic strains of LAB were isolated. The strains, showing broad spectrum of antimicrobial activity against food spoiling microorganisms, were selected. The genotyping by 16S rRNA sequencing, GS-PCR, RAPD PCR methods showed that they were presented by Lactobacillus rhamnosus109, L.plantarum 65, L.plantarum 66 and Enterococcus faecium 64 species. LAB are deposited in "Microbial Depository Center" (MDC) SPC "Armbiotechnology". Methods: LAB strains were isolated from different dairy products from rural households from the highland regions of Armenia. Serially diluted samples were spread on MRS (Merck, Germany) and hydrolyzed milk agar (1,2 % w/v). Single colonies from each LAB were individually inoculated in liquid MRS medium and incubated at 37oC for 24 hours. Culture broth with biomass was centrifuged at 10,000 g during 20 min for obtaining of cell free culture broth (CFC). The antimicrobial substances from CFC broth were purified by the combination of adsorption-desorption and ion-exchange chromatography methods. Separation of bacteriocins was performed using a HPLC method on "Avex ODS" C18 column. Mass analysis of peptides recorded on the device API 4000 in the electron ionization mode. The spot-on-lawn method on the test culture plated in the solid medium was applied. The antimicrobial activity is expressed in arbitrary units (AU/ml). Results. Purification of CFC broth of LAB allowed to obtain partially purified antimicrobial preparations which contains bacteriocins with broad spectrum of antimicrobial activity. Investigation of their main biochemical properties shown, that inhibitory activity of preparations is partially reduced after treatment with proteinase K, trypsin, pepsin, suggesting a proteinaceous nature of bacteriocin-like substances containing in CFC broth. Preparations preserved their activity after heat treatment (50-121 oC, 20 min) and were stable in the pH range 3–8. The results of SDS PAAG electrophoresis show that L.plantarum 66 and Ent.faecium 64 strains have one bacteriocin (BCN) with maximal antimicrobial activity with approximate molecular weight 2.0-3.0 kDa. From L.rhamnosus 109 two BCNs were obtained. Mass spectral analysis indicates that these bacteriocins have peptide bonds and molecular weight of BCN 1 and BCN 2 are approximately 1.5 kDa and 700 Da. Discussion: Thus, our experimental data shown, that isolated endemic strains of LAB are able to produce bacteriocins with high and different inhibitory activity against broad spectrum of microorganisms of different taxonomic group, such as Salmonella sp., Esherichia coli, Bacillus sp., L.monocytogenes, Proteus mirabilis, Staph. aureus, Ps. aeruginosa. Obtained results proved the perspectives for use of endemic strains in the preservation of foodstuffs. Acknowledgments: This work was realized with financial support of the Project Global Initiatives for Preliferation Prevention (GIPP) T2- 298, ISTC A-1866.

Keywords: antimicrobial activity, bacteriocins, endemic strains, food safety

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40 A Compact Standing-Wave Thermoacoustic Refrigerator Driven by a Rotary Drive Mechanism

Authors: Kareem Abdelwahed, Ahmed Salama, Ahmed Rabie, Ahmed Hamdy, Waleed Abdelfattah, Ahmed Abd El-Rahman

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Conventional vapor-compression refrigeration systems rely on typical refrigerants, such as CFC, HCFC and ammonia. Despite of their suitable thermodynamic properties and their stability in the atmosphere, their corresponding global warming potential and ozone depletion potential raise concerns about their usage. Thus, the need for new refrigeration systems, which are environment-friendly, inexpensive and simple in construction, has strongly motivated the development of thermoacoustic energy conversion systems. A thermoacoustic refrigerator (TAR) is a device that is mainly consisting of a resonator, a stack and two heat exchangers. Typically, the resonator is a long circular tube, made of copper or steel and filled with Helium as a the working gas, while the stack has short and relatively low thermal conductivity ceramic parallel plates aligned with the direction of the prevailing resonant wave. Typically, the resonator of a standing-wave refrigerator has one end closed and is bounded by the acoustic driver at the other end enabling the propagation of half-wavelength acoustic excitation. The hot and cold heat exchangers are made of copper to allow for efficient heat transfer between the working gas and the external heat source and sink respectively. TARs are interesting because they have no moving parts, unlike conventional refrigerators, and almost no environmental impact exists as they rely on the conversion of acoustic and heat energies. Their fabrication process is rather simpler and sizes span wide variety of length scales. The viscous and thermal interactions between the stack plates, heat exchangers' plates and the working gas significantly affect the flow field within the plates' channels, and the energy flux density at the plates' surfaces, respectively. Here, the design, the manufacture and the testing of a compact refrigeration system that is based on the thermoacoustic energy-conversion technology is reported. A 1-D linear acoustic model is carefully and specifically developed, which is followed by building the hardware and testing procedures. The system consists of two harmonically-oscillating pistons driven by a simple 1-HP rotary drive mechanism operating at a frequency of 42Hz -hereby, replacing typical expensive linear motors and loudspeakers-, and a thermoacoustic stack within which the energy conversion of sound into heat is taken place. Air at ambient conditions is used as the working gas while the amplitude of the driver's displacement reaches 19 mm. The 30-cm-long stack is a simple porous ceramic material having 100 square channels per square inch. During operation, both oscillating-gas pressure and solid-stack temperature are recorded for further analysis. Measurements show a maximum temperature difference of about 27 degrees between the stack hot and cold ends with a Carnot coefficient of performance of 11 and estimated cooling capacity of five Watts, when operating at ambient conditions. A dynamic pressure of 7-kPa-amplitude is recorded, yielding a drive ratio of 7% approximately, and found in a good agreement with theoretical prediction. The system behavior is clearly non-linear and significant non-linear loss mechanisms are evident. This work helps understanding the operation principles of thermoacoustic refrigerators and presents a keystone towards developing commercial thermoacoustic refrigerator units.

Keywords: refrigeration system, rotary drive mechanism, standing-wave, thermoacoustic refrigerator

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