Search results for: Townsend breakdown mechanism
2226 Analyzing the Evolution and Maturation of Bitcoin Improvement Proposals
Authors: Rodrigo Costa, Thomas Mazzuchi, Shahram Sarkani
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This study analyzes the evolution of Bitcoin Improvement Proposals (BIPs), the self-governing mechanism that enables updates to the Bitcoin protocol. By modeling BIP submission frequencies with a Negative Binomial distribution and detecting change points with the Pelt Rupture model, we identify three distinct intervals of proposal activity, suggesting shifts in development priorities over time. Long-term growth patterns, captured by Gompertz and Weibull models, indicate an S-shaped trend in cumulative BIP counts, pointing toward a maturation phase in Bitcoin’s protocol. Our findings suggest that Bitcoin may be entering a stable stage, with fewer fundamental changes and more incremental enhancements. This trend highlights the need for further research into BIP content and more studies into its dynamics to better understand decentralized protocol governance and maturation.Keywords: bitcoin improvement proposals, innovation management, change point detection, systems modeling, simulation
Procedia PDF Downloads 52225 Synthesis of NiO and ZnO Nanoparticles and Charactiration for the Eradication of Lead (Pb) from Wastewater
Authors: Sadia Ata, Anila Tabassum, Samina ghafoor, Ijaz ul Mohsin, Azam Muktar
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Heavy metal ions such as Pb2+, Cd2+, Zn2+, Ni2+ and Hg2+, in wastewater are considered as the serious environmental problem. Among these heavy metals, Lead or Pb (II) is the most toxic heavy metal. Exposure to lead causes damage of nervous system, mental retardation, renal kidney disease, anemia and cancer in human beings. Adsorption is the most widely used method to remove metal ions based on the physical interaction between metal ions and sorbents. With the development of nanotechnology, nano-sized materials are proved to be effective sorbents for the removal of heavy metal ions from wastewater due to their unique structural properties. The present work mainly focuses on the synthesis of NiO and ZnO nanoparticles for the removal of Lead ions, their preparation, characterization by XRD, FTIR, SEM, and TEM, adsorption characteristics and mechanism, along with adsorption isotherm model and adsorption kinetics to understand the adsorption procedure.Keywords: heavy metal, adsorption isotherms, nanoparticles, wastewater
Procedia PDF Downloads 5892224 The Reflection of Greek Reality Concerning Taxation from the Perspective of Both Tax Payers and Taxmen
Authors: Evagelia Makri, Maria Tsourela, Dimitris Paschaloudis, Dafni M. Nerantzaki
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One of the biggest financial and social problems, which at the same time constitute one of the greater challenges that Greek society faces today, is the illegal avoidance of tax payments. Tax evasion may negate financial data and community budgets, as well as breed financial chaos. This research seeks to reflect Greek reality concerning tax measures. Also, there will be an effort to record the factors surrounding tax evasion. Greek tax system’s data will be rendered in financial terms. Questionnaires will be handed out to tax payers, and interviews will be conducted to taxmen. The quantitative analysis of the questionnaire answers will define the tax payers’ opinion towards the existence of tax evasion. The qualitative analysis of the interviews will reveal the main reason that boosts tax evasion. At the end, there will be some realistic proposals about how to better collect taxes, through the creation of a strong regulatory mechanism.Keywords: tax evasion, tax collection measures, insurance recovery measures, Greek tax system
Procedia PDF Downloads 3632223 Mutational Analysis of JAK2V617F in Tunisian CML Patients with TKI-Resistance
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Background:Chronicmyeloidleukemia (CML), a hematologicaldisease, ischaracterized by t (9; 22) and relatedoncogene BCR-ABL formation. Although Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML, resistanceoccurs and possibly médiates by mutation in severalgenesindependently of the bcr-abl1 kinase mechanism. it has been reportedthat JAK2V617F/BCR-ABL double positivitymaybe a potential marker of resistance in CML. Aims: This studywasinvestigated the JAK2V617F mutation in TKI-resistant CML patients. Methods: A retrospectivestudywasconducted in the Hospital University of Sfax, south of Tunisia, including all CML TKI-resistant patients. A Sanger sequencingwasperformedusing a high-fidelity DNA polymerase. Results:Nineresistant CP-CML patients wereenrolled in thisstudy. The JAK2V617F mutation wasdetectedin 3 patients with TKI resistance. Conclusion:Despite the limit of ourstudy, ourfinding highlights the high frequency of JAK2V617F/BCR-ABL double positivity as an important marker of resistance. So; the combination of JAK and TKI inhibitorsmightbe effective and potentiallybeguided by molecular monitoring of minimal residual disease1.Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, resistance, JAK2V617F, BCR-ABL
Procedia PDF Downloads 672222 Study the Influence of Zn in Zn-MgFe₂O₄ Nanoparticles for CO₂ Gas Sensors
Authors: Maryam Kiani, Xiaoqin Tian, Yu Du, Abdul Basit Kiani
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Zn-doped MgFe₂O₄ nanoparticles (ZMFO) (Zn=0.0, 0.2, 0.35, 0.5,) were prepared by Co-precipitation synthesis route. Structural and morphological analysis confirmed the formation of spinel cubic nanostructure by X-Ray diffraction (XRD) data shows high reactive surface area owing to a small average particle size of about 14 nm, which greatly influences the gas sensing mechanism. The gas sensing property of ZMFO for several gases was obtained by measuring the resistance as a function of different factors, like composition and response time in air and in the presence of gas. The sensitivity of spinel ferrite to gases CO₂, O₂, and O₂ at room temperature has been compared. The nanostructured ZMFO exhibited high sensitivity in the order of CO₂>O₂ and showed a good response time of (~1min) to CO₂, demonstrating that this expanse of research can be used in the field of gas sensors devising high sensitivity and good selectivity at 25°C.Keywords: MgFe₂O₄ nanoparticles, hydrothermal synthesis, gas sensing properties, XRD
Procedia PDF Downloads 1182221 Analytical Similarity Assessment of Bevacizumab Biosimilar Candidate MB02 Using Multiple State-of-the-Art Assays
Authors: Marie-Elise Beydon, Daniel Sacristan, Isabel Ruppen
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MB02 (Alymsys®) is a candidate biosimilar to bevacizumab, which was developed against the reference product (RP) Avastin® sourced from both the European Union (EU) and United States (US). MB02 has been extensively characterized comparatively to Avastin® at a physicochemical and biological level using sensitive orthogonal state-of-the-art analytical methods. MB02 has been demonstrated similar to the RP with regard to its primary and higher-order structure, post- and co-translational profiles such as glycosylation, charge, and size variants. Specific focus has been put on the characterization of Fab-related activities, such as binding to VEGF A 165, which directly reflect the bevacizumab mechanism of action. Fc-related functionality was also investigated, including binding to FcRn, which is indicative of antibodies' half-life. The data generated during the analytical similarity assessment demonstrate the high analytical similarity of MB02 to its RP.Keywords: analytical similarity, bevacizumab, biosimilar, MB02
Procedia PDF Downloads 2882220 Virtual Container Yard: A Paradigm Shift in Container Inventory Management
Authors: Lalith Edirisinghe, Zhihong Jin, A.W. Wijeratne, Hansa Edirisinghe, Lakshmi Ranwala Rashika Mudunkotuwa
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A paradigm shift in container inventory management (CIM) is a long-awaited industry need. Virtual container yard (VCY) is a concept developed in 2013 and its primary objective is to minimize shipping transport cost through implementing container exchange between carriers. Shipping lines always try to maintain lower container idle time and provide higher customer satisfaction. However, it is disappointing to note that carriers turn a blind eye to the escalating cost resulted from the present inefficient CIM mechanism. The cost of empty container management is simply transferred to the importers and exporters as freight adjustments. It also creates an environmental hazard. Therefore, it has now become a problem for the society. Therefore, a paradigm shift may be required as the present CIM system is not working for common interests of human beings as it should be.Keywords: collaboation, inventory, shipping, virtual container yard
Procedia PDF Downloads 2632219 A Hybrid LES-RANS Approach to Analyse Coupled Heat Transfer and Vortex Structures in Separated and Reattached Turbulent Flows
Authors: C. D. Ellis, H. Xia, X. Chen
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Experimental and computational studies investigating heat transfer in separated flows have been of increasing importance over the last 60 years, as efforts are being made to understand and improve the efficiency of components such as combustors, turbines, heat exchangers, nuclear reactors and cooling channels. Understanding of not only the time-mean heat transfer properties but also the unsteady properties is vital for design of these components. As computational power increases, more sophisticated methods of modelling these flows become available for use. The hybrid LES-RANS approach has been applied to a blunt leading edge flat plate, utilising a structured grid at a moderate Reynolds number of 20300 based on the plate thickness. In the region close to the wall, the RANS method is implemented for two turbulence models; the one equation Spalart-Allmaras model and Menter’s two equation SST k-ω model. The LES region occupies the flow away from the wall and is formulated without any explicit subgrid scale LES modelling. Hybridisation is achieved between the two methods by the blending of the nearest wall distance. Validation of the flow was obtained by assessing the mean velocity profiles in comparison to similar studies. Identifying the vortex structures of the flow was obtained by utilising the λ2 criterion to identify vortex cores. The qualitative structure of the flow compared with experiments of similar Reynolds number. This identified the 2D roll up of the shear layer, breaking down via the Kelvin-Helmholtz instability. Through this instability the flow progressed into hairpin like structures, elongating as they advanced downstream. Proper Orthogonal Decomposition (POD) analysis has been performed on the full flow field and upon the surface temperature of the plate. As expected, the breakdown of POD modes for the full field revealed a relatively slow decay compared to the surface temperature field. Both POD fields identified the most energetic fluctuations occurred in the separated and recirculation region of the flow. Latter modes of the surface temperature identified these levels of fluctuations to dominate the time-mean region of maximum heat transfer and flow reattachment. In addition to the current research, work will be conducted in tracking the movement of the vortex cores and the location and magnitude of temperature hot spots upon the plate. This information will support the POD and statistical analysis performed to further identify qualitative relationships between the vortex dynamics and the response of the surface heat transfer.Keywords: heat transfer, hybrid LES-RANS, separated and reattached flow, vortex dynamics
Procedia PDF Downloads 2312218 An Evolutionary Algorithm for Optimal Fuel-Type Configurations in Car Lines
Authors: Charalampos Saridakis, Stelios Tsafarakis
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Although environmental concern is on the rise across Europe, current market data indicate that adoption rates of environmentally friendly vehicles remain extremely low. Against this background, the aim of this paper is to a) assess preferences of European consumers for clean-fuel cars and their characteristics and b) design car lines that optimize the combination of fuel types among models in the line-up. In this direction, the authors introduce a new evolutionary mechanism and implement it to stated-preference data derived from a large-scale choice-based conjoint experiment that measures consumer preferences for various factors affecting clean-fuel vehicle (CFV) adoption. The proposed two-step methodology provides interesting insights into how new and existing fuel-types can be combined in a car line that maximizes customer satisfaction.Keywords: clean-fuel vehicles, product line design, conjoint analysis, choice experiment, differential evolution
Procedia PDF Downloads 2792217 Addressing Supply Chain Data Risk with Data Security Assurance
Authors: Anna Fowler
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When considering assets that may need protection, the mind begins to contemplate homes, cars, and investment funds. In most cases, the protection of those assets can be covered through security systems and insurance. Data is not the first thought that comes to mind that would need protection, even though data is at the core of most supply chain operations. It includes trade secrets, management of personal identifiable information (PII), and consumer data that can be used to enhance the overall experience. Data is considered a critical element of success for supply chains and should be one of the most critical areas to protect. In the supply chain industry, there are two major misconceptions about protecting data: (i) We do not manage or store confidential/personally identifiable information (PII). (ii) Reliance on Third-Party vendor security. These misconceptions can significantly derail organizational efforts to adequately protect data across environments. These statistics can be exciting yet overwhelming at the same time. The first misconception, “We do not manage or store confidential/personally identifiable information (PII)” is dangerous as it implies the organization does not have proper data literacy. Enterprise employees will zero in on the aspect of PII while neglecting trade secret theft and the complete breakdown of information sharing. To circumvent the first bullet point, the second bullet point forges an ideology that “Reliance on Third-Party vendor security” will absolve the company from security risk. Instead, third-party risk has grown over the last two years and is one of the major causes of data security breaches. It is important to understand that a holistic approach should be considered when protecting data which should not involve purchasing a Data Loss Prevention (DLP) tool. A tool is not a solution. To protect supply chain data, start by providing data literacy training to all employees and negotiating the security component of contracts with vendors to highlight data literacy training for individuals/teams that may access company data. It is also important to understand the origin of the data and its movement to include risk identification. Ensure processes effectively incorporate data security principles. Evaluate and select DLP solutions to address specific concerns/use cases in conjunction with data visibility. These approaches are part of a broader solutions framework called Data Security Assurance (DSA). The DSA Framework looks at all of the processes across the supply chain, including their corresponding architecture and workflows, employee data literacy, governance and controls, integration between third and fourth-party vendors, DLP as a solution concept, and policies related to data residency. Within cloud environments, this framework is crucial for the supply chain industry to avoid regulatory implications and third/fourth party risk.Keywords: security by design, data security architecture, cybersecurity framework, data security assurance
Procedia PDF Downloads 882216 Graft Copolymerization of Cellulose Acetate with Nitro-N-Amino Phenyl Maleimides
Authors: Azza. A. Al-Ghamdi, Abir. A. Abdel-Naby
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The construction of Nitro -N-amino phenyl maleimide branches onto Cellulose acetate (CA) substrate by free radical graft copolymerization using benzoyl peroxide as initiator led to formation of highly thermal stable copolymers as shown from the results of gravimetric analysis (TGA). CA-g-2,4-dinitro amino phenyl maleimide exhibited higher thermal stability than the CA-g-4-nitro amino phenyl maleimide as shown from the initial decomposition temperature (To). This is due to the ability of nitro group to form hydrogen bonding with hydroxyl group of the glucopyranose ring which increases the crystallinity of polymeric matrix. The crystalline shapes representing the graft part are clearly distinct in the Emission scanning electron microscope (ESEM) morphology of the copolymer. A suggested reaction mechanism for the grafting process was also discussed.Keywords: Cellulose acetate, Crystallinity, Graft copolymerization, Thermal properties
Procedia PDF Downloads 1622215 A Study on the Influence of Annealing Conditions on the Properties of ZnON Thin Films
Authors: Kiran Jose, Anjana J. G., Venu Anand, Aswathi R. Nair
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This work investigates the change in structural, optical, and electrical properties of Zinc Oxynitride (ZnON) thin film when annealed in different atmospheres. ZnON film is prepared by reactively sputtering the Zinc target using argon, oxygen, and nitrogen. The deposited film is annealed for one hour at 3250C in the Vaccum condition and Nitrogen and oxygen atmospheres. XRD and Raman spectroscopy is used to study the structural properties of samples. The current conduction mechanism is examined by extracting voltage versus current characteristics on a logarithmic scale, and the optical response is quantified by analyzing persistent photoconductivity (PPC) behavior. This study proposes the optimum annealing atmosphere for ZnON thin film for a better transistor and photosensor application.Keywords: Zinc oxynitride, thin film, annealing, DC sputtering
Procedia PDF Downloads 932214 An AK-Chart for the Non-Normal Data
Authors: Chia-Hau Liu, Tai-Yue Wang
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Traditional multivariate control charts assume that measurement from manufacturing processes follows a multivariate normal distribution. However, this assumption may not hold or may be difficult to verify because not all the measurement from manufacturing processes are normal distributed in practice. This study develops a new multivariate control chart for monitoring the processes with non-normal data. We propose a mechanism based on integrating the one-class classification method and the adaptive technique. The adaptive technique is used to improve the sensitivity to small shift on one-class classification in statistical process control. In addition, this design provides an easy way to allocate the value of type I error so it is easier to be implemented. Finally, the simulation study and the real data from industry are used to demonstrate the effectiveness of the propose control charts.Keywords: multivariate control chart, statistical process control, one-class classification method, non-normal data
Procedia PDF Downloads 4222213 Synthesize of Cobalt Oxide Nanoballs/Carbon Aerogel Nanostructures: Towards High-Performance Materials for Supercapacitors
Authors: A. Bahadoran, M. Zomorodian
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The synthesizer of cobalt oxide nanoballs (length 3−4 μm, width 250−400 nm) was achieved by a simple high-temperature supercritical solution method. Multiwalled carbon aerogels are a step towards high-density nanometer-scale nanostructures. Cobalt oxide nanoballs were prepared by supercritical solution method. Synthesis in an aqueous solution containing cobalt hydroxide at ∼80 °C without any further heat treatment at high temperature. The formation of cobalt oxide nanoballs on carbon aerogel was confirmed by X-ray diffraction and Raman spectroscopy. The FE-SEM images showed the presence of cobalt oxide nanoballs. The reaction mechanism of the ultrasound-assisted synthesis of cobalt oxide nanostructures was proposed on the basis of the XRD, X-ray absorption spectroscopy analysis and FE-SEM observation of the reaction products taken during the course of the synthesis.Keywords: cobalt oxide nano balls, carbon aerogel, synthesize, nanostructure
Procedia PDF Downloads 3582212 Molecular Dynamics Simulation Study of the Influence of Potassium Salts on the Adsorption and Surface Hydration Inhibition Performance of Hexane, 1,6 - Diamine Clay Mineral Inhibitor onto Sodium Montmorillonite
Authors: Justine Kiiza, Xu Jiafang
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The world’s demand for energy is increasing rapidly due to population growth and a reduction in shallow conventional oil and gas reservoirs, resorting to deeper and mostly unconventional reserves like shale oil and gas. Most shale formations contain a large amount of expansive sodium montmorillonite (Na-Mnt), due to high water adsorption, hydration, and when the drilling fluid filtrate enters the formation with high Mnt content, the wellbore wall can be unstable due to hydration and swelling, resulting to shrinkage, sticking, balling, time wasting etc., and well collapse in extreme cases causing complex downhole accidents and high well costs. Recently, polyamines like 1, 6 – hexane diamine (HEDA) have been used as typical drilling fluid shale inhibitors to minimize and/or cab clay mineral swelling and maintain the wellbore stability. However, their application is limited to shallow drilling due to their sensitivity to elevated temperature and pressure. Inorganic potassium salts i.e., KCl, have long been applied for restriction of shale formation hydration expansion in deep wells, but their use is limited due to toxicity. Understanding the adsorption behaviour of HEDA on Na-Mnt surfaces in present of organo-salts, organic K-salts e.g., HCO₂K - main component of organo-salt drilling fluid, is of great significance in explaining the inhibitory performance of polyamine inhibitors. Molecular dynamic simulations (MD) were applied to investigate the influence of HCO₂K and KCl on the adsorption mechanism of HEDA on the Na-Mnt surface. Simulation results showed that adsorption configurations of HEDA are mainly by terminal amine groups with a flat-lying alkyl hydrophobic chain. Its interaction with the clay surface decreased the H-bond number between H₂O-clay and neutralized the negative charge of the Mnt surface, thus weakening the surface hydration ability of Na-Mnt. The introduction of HCO₂K greatly improved inhibition ability, coordination of interlayer ions with H₂O as they were replaced by K+, and H₂O-HCOO- coordination reduced H₂O-Mnt interactions, mobility and transport capability of H₂O molecules were more decreased. While KCl showed little ability and also caused more hydration with time, HCO₂K can be used as an alternative for offshore drilling instead of toxic KCl, with a maximum concentration noted in this study as 1.65 wt%. This study provides a theoretical elucidation for the inhibition mechanism and adsorption characteristics of HEDA inhibitor on Na-Mnt surfaces in the presence of K+-salts and may provide more insight into the evaluation, selection, and molecular design of new clay-swelling high-performance WBDF systems used in oil and gas complex offshore drilling well sections.Keywords: shale, hydration, inhibition, polyamines, organo-salts, simulation
Procedia PDF Downloads 472211 Electret: A Solution of Partial Discharge in High Voltage Applications
Authors: Farhina Haque, Chanyeop Park
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The high efficiency, high field, and high power density provided by wide bandgap (WBG) semiconductors and advanced power electronic converter (PEC) topologies enabled the dynamic control of power in medium to high voltage systems. Although WBG semiconductors outperform the conventional Silicon based devices in terms of voltage rating, switching speed, and efficiency, the increased voltage handling properties, high dv/dt, and compact device packaging increase local electric fields, which are the main causes of partial discharge (PD) in the advanced medium and high voltage applications. PD, which occurs actively in voids, triple points, and airgaps, is an inevitable dielectric challenge that causes insulation and device aging. The aging process accelerates over time and eventually leads to the complete failure of the applications. Hence, it is critical to mitigating PD. Sharp edges, airgaps, triple points, and bubbles are common defects that exist in any medium to high voltage device. The defects are created during the manufacturing processes of the devices and are prone to high-electric-field-induced PD due to the low permittivity and low breakdown strength of the gaseous medium filling the defects. A contemporary approach of mitigating PD by neutralizing electric fields in high power density applications is introduced in this study. To neutralize the locally enhanced electric fields that occur around the triple points, airgaps, sharp edges, and bubbles, electrets are developed and incorporated into high voltage applications. Electrets are electric fields emitting dielectric materials that are embedded with electrical charges on the surface and in bulk. In this study, electrets are fabricated by electrically charging polyvinylidene difluoride (PVDF) films based on the widely used triode corona discharge method. To investigate the PD mitigation performance of the fabricated electret films, a series of PD experiments are conducted on both the charged and uncharged PVDF films under square voltage stimuli that represent PWM waveform. In addition to the use of single layer electrets, multiple layers of electrets are also experimented with to mitigate PD caused by higher system voltages. The electret-based approach shows great promise in mitigating PD by neutralizing the local electric field. The results of the PD measurements suggest that the development of an ultimate solution to the decades-long dielectric challenge would be possible with further developments in the fabrication process of electrets.Keywords: electrets, high power density, partial discharge, triode corona discharge
Procedia PDF Downloads 2032210 Strength Translation from Spun Yarns to Woven Fabrics
Authors: Anindya Ghosh
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Structural parameters, yarn to yarn friction, strength of ring, rotor, air-jet and open-end friction spun yarns and the strength of fabrics made from these yarns are measured. The ratio of fabric strip strength per yarn and corresponding single yarn strength is considered as a measure of quantifying the fabric assistance. Mechanism of yarn failure inside the fabric is different as that of single yarn and the former exhibit more fibre rupture. Fabrics made from weaker yarns have higher ratio of strip strength to single yarn strength than that made from stronger yarns due to larger increase in the percentage of rupture fibres in the former. The fabric assistance also depends to some extent on the degree of gripping of the yarns that is influenced by the yarn to yarn friction, extent of yarn flattening and yarn diameter.Keywords: fabric assistance, fabric strength, yarn diameter, yarn friction, yarn strength
Procedia PDF Downloads 2492209 A Comparison Study of Fabric Objective Measurement (FOM) Using KES-FB and PhabrOmeter System on Warp Knitted Fabrics Handle: Smoothness, Stiffness and Softness
Authors: Ka-Yan Yim, Chi-Wai Kan
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This paper conducts a comparison study using KES-FB and PhabrOmeter to measure 58 selected warp knitted fabric hand properties. Fabric samples were selected and measured by both KES-FB and PhabrOmeter. Results show differences between these two measurement methods. Smoothness and stiffness values obtained by KES-FB were found significant correlated (p value = 0.003 and 0.022) to the PhabrOmeter results while softness values between two measurement methods did not show significant correlation (p value = 0.828). Disagreements among these two measurement methods imply limitations on different mechanism principles when facing warp knitted fabrics. Subjective measurement methods and further studies are suggested in order to ascertain deeper investigation on the mechanisms of fabric hand perceptions.Keywords: fabric hand, fabric objective measurement, KES-FB, PhabrOmeter
Procedia PDF Downloads 2092208 A Unified Model for Orotidine Monophosphate Synthesis: Target for Inhibition of Growth of Mycobacterium tuberculosis
Authors: N. Naga Subrahmanyeswara Rao, Parag Arvind Deshpande
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Understanding nucleotide synthesis reaction of any organism is beneficial to know the growth of it as in Mycobacterium tuberculosis to design anti TB drug. One of the reactions of de novo pathway which takes place in all organisms was considered. The reaction takes places between phosphoribosyl pyrophosphate and orotate catalyzed by orotate phosphoribosyl transferase and divalent metal ion gives orotdine monophosphate, a nucleotide. All the reaction steps of three experimentally proposed mechanisms for this reaction were considered to develop kinetic rate expression. The model was validated using the data for four organisms. This model could successfully describe the kinetics for the reported data. The developed model can serve as a reliable model to describe the kinetics in new organisms without the need of mechanistic determination. So an organism-independent model was developed.Keywords: mechanism, nucleotide, organism, tuberculosis
Procedia PDF Downloads 3342207 Mechanisms of O-1602 Induced Endothelium-Independent Vasorelaxation of Rat Small Mesenteric Artery
Authors: Yousuf Al Suleimani, Ahmed Al Mahruqi
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A typical cannabinoid O-1602 induces vasorelaxation and activates the orphan G protein-coupled receptor GPR55 in human endothelial cells. The aim of this study is to characterize the mechanisms of endothelium-independent relaxation of O-1602 in the rat small mesenteric artery using wire myograph. In endothelium-denuded vessels, O-1602 partially produced concentration-dependent vasorelaxation. In vessels depleted of intracellular Ca2+ (by EGTA and methoxamine), CaCl2 produced concentration-dependent contraction. Preincubation with O-1602 (at 10 µM and 30 µM) abolished the contractile responses (P<0.01). The putative antagonist at novel “endothelial anandamide receptor” O-1918 (10 µM) significantly reversed the inhibitory effect of O-1602 on CaCl2-induced vasoconstriction. It is likely that the mechanism of endothelium-independent vasorelaxation to O-1602 is mediated by interfering with Ca2+ entry via an O-1918-sensitive pathway.Keywords: O-1602, endothelium, vasorelaxation, calcium
Procedia PDF Downloads 3592206 Elucidation of the Photoreactivity of 2-Hydroxychalcones and the Effect of Continuous Photoflow Method on the Photoreactivity
Authors: Sobiya George, Anna Dora Gudmundsdottir
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The 2-hydroxychalcones form an important group of organic compounds not only because of their pharmacological properties but also because they are intermediates in the biosynthesis of flavanones. We studied the photoreactivity of 2-hydroxychalcone derivatives in aprotic solvent acetonitrile and found that their photochemistry is concentration-dependent. Irradiation of 2-hydroxychalcone derivatives with 365 nm light emitting diode (LED) in dilute concentration selectively forms flavanones, whereas, at higher concentrations, an additional photoproduct is observed. However, the application of the continuous photo-flow method resulted in the selective formation of flavanones even at higher concentrations. To understand the reaction mechanism and explain the concentration-dependent photoreactivity of 2-hydroxychalcones, we preformed trapping studies with tris(trimethylsilyl)silane, nanosecond laser flash photolysis, and time dependent-density functional theory (TD-DFT) calculations.Keywords: flavanones, hydroxychalcones, laser flash photolysis, TD-DFT calculations
Procedia PDF Downloads 1492205 Health Payments and Household Wellbeing in India: Examining the Role of Health Policy Interventions
Authors: Shailender Kumar
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Current health policy pronouncements in India advocate for insurance-based financing mechanism to achieve universal health coverage (UHC), while undermine the role of comprehensive healthcare provision system. UHC is achieved when all people receive the health services they need without suffering financial hardship. This study, using 68th & 71st NSS rounds data, examines their relative and combined strength in achieving the above objective. Health-insurance has been unsuccessful in reducing prevalence and catastrophic effects of out-of-pocket payment and even dismantle the effectiveness of traditional way of health financing system. Healthcare provision is the best way forward to enhance health and well-being of households in condition if India removes existing inadequacies and inequalities in service provision across districts/states and ensure free/low cost medicines/diagnostics to the citizens.Keywords: health policy, demand-side financing, supply-side financing, incidence of health payment
Procedia PDF Downloads 2592204 Comparative International Law and Feminist Legal Studies, Uniting to Make a Difference in Addressing the Disempowerment of Women
Authors: Isaac Kfir
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In thinking about the role of the law and its impact on socially constructed norms and identities, scholars have come to explore a multitude of issues to do with equality, empowerment, and views. The aim of this contribution is threefold. Firstly, offer a descriptive framework of feminist legal studies (FLS) through a review of the evolution of the field in the context of equality, rights, and justice. Secondly, encourage those working on equality, rights, and justice in respect to ‘women’s issues’ to engage in international comparative legal studies. Third, to highlight that those seeking solutions to disempowerment and discrimination must recognize that they need to contend with claims that one is seeking to undermine cultural norms. Therefore, one effective way for feminists to address this situation is by relying more on the international legal mechanism, which reflects basic legal tenets as to the universality of equality, rights, and justice, that can then help shape the domestic setting.Keywords: international comparative law, feminist legal studies, equality, rights, justice
Procedia PDF Downloads 2762203 Toward Understanding the Glucocorticoid Receptor Network in Cancer
Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden
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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor
Procedia PDF Downloads 2272202 Improving the Biocontrol of the Argentine Stem Weevil; Using the Parasitic Wasp Microctonus hyperodae
Authors: John G. Skelly, Peter K. Dearden, Thomas W. R. Harrop, Sarah N. Inwood, Joseph Guhlin
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The Argentine stem weevil (ASW; L. bonariensis) is an economically important pasture pest in New Zealand, which causes about $200 million of damage per annum. Microctonus hyperodae (Mh), a parasite of the ASW in its natural range in South America, was introduced into New Zealand to curb the pasture damage caused by the ASW. Mh is an endoparasitic wasp that lays its eggs in the ASW halting its reproduction. Mh was initially successful at preventing ASW proliferation and reducing pasture damage. The effectiveness of Mh has since declined due to decreased parasitism rates and has resulted in increased pasture damage. Although the mechanism through which ASW has developed resistance to Mh has not been discovered, it has been proposed to be due to the different reproductive modes used by Mh and the ASW in New Zealand. The ASW reproduces sexually, whereas Mh reproduces asexually, which has been hypothesised to have allowed the ASW to ‘out evolve’ Mh. Other species within the Microctonus genus reproduce both sexually and asexually. Strains of Microctonus aethiopoides (Ma), a species closely related to Mh, reproduce either by sexual or asexual reproduction. Comparing the genomes of sexual and asexual Microctonus may allow for the identification of the mechanism of asexual reproduction and other characteristics that may improve Mh as a biocontrol agent. The genomes of Mh and three strains of Ma, two of which reproduce sexually and one reproduces asexually, have been sequenced and annotated. The French (MaFR) and Moroccan (MaMO) reproduce sexually, whereas the Irish strain (MaIR) reproduces asexually. Like Mh, The Ma strains are also used as biocontrol agents, but for different weevil species. The genomes of Mh and MaIR were subsequently upgraded using Hi-C, resulting in a set of high quality, highly contiguous genomes. A subset of the genes involved in mitosis and meiosis, which have been identified though the use of Hidden Markov Models generated from genes involved in these processes in other Hymenoptera, have been catalogued in Mh and the strains of Ma. Meiosis and mitosis genes were broadly conserved in both sexual and asexual Microctonus species. This implies that either the asexual species have retained a subset of the molecular components required for sexual reproduction or that the molecular mechanisms of mitosis and meiosis are different or differently regulated in Microctonus to other insect species in which these mechanisms are more broadly characterised. Bioinformatic analysis of the chemoreceptor compliment in Microctonus has revealed some variation in the number of olfactory receptors, which may be related to host preference. Phylogenetic analysis of olfactory receptors highlights variation, which may be able to explain different host range preferences in the Microctonus. Hi-C clustering implies that Mh has 12 chromosomes, and MaIR has 8. Hence there may be variation in gene regulation between species. Genome alignment of Mh and MaIR implies that there may be large scale genome structural variation. Greater insight into the genetics of these agriculturally important group of parasitic wasps may be beneficial in restoring or maintaining their biocontrol efficacy.Keywords: argentine stem weevil, asexual, genomics, Microctonus hyperodae
Procedia PDF Downloads 1562201 Elucidation of Dynamics of Murine Double Minute 2 Shed Light on the Anti-cancer Drug Development
Authors: Nigar Kantarci Carsibasi
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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.Keywords: cancer, drug design, elastic network model, MDM2
Procedia PDF Downloads 1302200 How to Ensure Environmental Sustainability and Food Security through the Use of Payments for Environmental Services in Developing Countries
Authors: Carlos Alves
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This research paper demonstrates how payments for environmental services (PES) can be an effective mechanism to combat food insecurity and reduce environmental degradation in developing countries. The paper begins by discussing how environmental services affect each one of the pillars of food security: availability, access, and utilization of food. However, due to numerous global environmental challenges, a new pillar of food security based on environmental sustainability is proposed and discussed. An argument is then made that PES can usefully combat food insecurity. It can provide an extra income to those who take on environmental service and help them to have a better access to food. In order to be successful in addressing food insecurity, PES schemes should target on the poor and redress issues that can prevent their effectiveness. Finally, the research presents a case study that discusses how several developing countries addressed problems and successfully developed PES programs.Keywords: environmental sustainability, food security, nutrition, payments for environmental services
Procedia PDF Downloads 3922199 Mechanism and Kinetic of Layers Growth: Application to Nitriding of 32CrMoV13 Steel
Authors: Torchane Lazhar
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In this work, our task consists in optimizing the nitriding treatment at low-temperature of the steel 32CrMoV13 by the way of the mixtures of ammonia gas, nitrogen and hydrogen to improve the mechanical properties of the surface (good wear resistance, friction and corrosion), and of the diffusion layer of the nitrogen (good resistance to fatigue and good tenacity with heart). By limiting our work to the pure iron and to the alloys iron-chromium and iron-chrome-carbon, we have studied the various parameters which manage the nitriding: flow rate and composition of the gaseous phase, the interaction chromium-nitrogen and chromium-carbon by the help of experiments of nitriding realized in the laboratory by thermogravimetry. The acquired knowledge have been applied by the mastery of the growth of the combination layer on the diffusion layer in the case of the industrial steel 32CrMoV13.Keywords: diffusion of nitrogen, gaseous nitriding, layer growth kinetic, steel
Procedia PDF Downloads 4122198 Gig Economy Development Trends in Georgia
Authors: Nino Grigolaia
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The paper discusses the importance of the development of the gig economy in the economy of Georgia, analyzes the trends of the development of the gig economy, and identifies the main challenges in this field. Objective. The objective of the study is to assess the role of the gig economy, identify the main challenges and develop recommendations. Methodologies. Analysis, synthesis, comparison, induction and other methods are used; A desk study has been conducted. Findings. The advantages and disadvantages of the gig economy are identified, and the impact of the changes caused by the development of the gig economy on labor relations and employment is determined. It is argued that the ongoing technological changes have led to the emergence of new global trends in the labor market and increased the inequality of income distribution. Conclusions. Based on the analysis of the gig economy in the world and in Georgia, relevant recommendations are proposed, namely: establishing a new system of regulating the incomes of employees in this field, developing a real social protection mechanism, Development of political and legal instruments for regulation of gig economy and others.Keywords: gig economy, economy of Georgia, digital platforms, labor relations
Procedia PDF Downloads 682197 Internet of Things: Route Search Optimization Applying Ant Colony Algorithm and Theory of Computer Science
Authors: Tushar Bhardwaj
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Internet of Things (IoT) possesses a dynamic network where the network nodes (mobile devices) are added and removed constantly and randomly, hence the traffic distribution in the network is quite variable and irregular. The basic but very important part in any network is route searching. We have many conventional route searching algorithms like link-state, and distance vector algorithms but they are restricted to the static point to point network topology. In this paper we propose a model that uses the Ant Colony Algorithm for route searching. It is dynamic in nature and has positive feedback mechanism that conforms to the route searching. We have also embedded the concept of Non-Deterministic Finite Automata [NDFA] minimization to reduce the network to increase the performance. Results show that Ant Colony Algorithm gives the shortest path from the source to destination node and NDFA minimization reduces the broadcasting storm effectively.Keywords: routing, ant colony algorithm, NDFA, IoT
Procedia PDF Downloads 444