Search results for: sliding mechanism

Authors: Petnamnueng Dettipponpong, Shuen E. Chen

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Heat stress is known to have negative effects on reproductive functions, such as follicular development and ovulation. This study aimed to investigate the specific effects of heat stress on steroid hormone secretion of ovarian follicle cells, particularly in relation to the expression of Apolipoprotein B (ApoB) and microsomal triglyceride transfer protein (MTP). The aim of the study was to understand the impact of heat stress on steroid hormone secretion in ovarian follicle cells and to explore the role of ApoB and MTP in this process. Primary granulosa and theca cells were collected from follicles and cultured under heat stress conditions (42 °C) for various time periods. Controls were maintained under normal conditions (37.5 °C ). The culture medium was collected at different time points to measure levels of progesterone and estradiol using ELISA kits. ApoB and MTP expression levels were analyzed using homemade antibodies and western blot. Data were assessed by a one-way ANOVA comparison test with Duncan’s new multiple-range test. Results were expressed as mean±S.E. Difference was considered significant at P<0.05. The results showed that heat stress significantly increased progesterone secretion in granulosa cells, with the peak observed after 13 hours of recovery under thermoneutral conditions. Estradiol secretion by theca cells was not affected. Heat stress also had a significant negative effect on granulosa cell viability. Additionally, the expression of ApoB and MTP was found to be differentially regulated by heat stress. ApoB expression in theca cells was transiently promoted, while ApoB expression in granulosa cells was consistently suppressed. MTP expression increased after 5 hours of recovery in both cell types. These findings suggest a mechanism by which chicken follicle cells export cellular lipids as very low-density lipoprotein (VLDL) in response to thermal stress. These contribute to our understanding of the role of ApoB and MTP steroidogenesis and lipid metabolism under heat stress conditions. The study involved the collection of primary granulosa and theca cells, culture under different temperature conditions, and analysis of the culture medium for hormone levels using ELISA kits. ApoB and MTP expression levels were assessed using homemade antibodies and western blot. This study aimed to address the effects of heat stress on steroid hormone secretion in ovarian follicle cells, as well as the role of ApoB and MTP in this process. The study demonstrates that heat stress stimulates steroidogenesis in granulosa cells, affecting progesterone secretion. ApoB and MTP expression were found to be differentially regulated by heat stress, indicating a potential mechanism for the export of cellular lipids in response to thermal stress.

Keywords: heat stress, granulosa cells, theca cells, steroidogenesis, chicken, apolipoprotein B, microsomal triglyceride transfer protein

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Authors: Mohsen Farshad

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Information and force definition has been intertwined with the concept of entropy for many years. The displacement information of degrees of freedom with Brownian motions at a given temperature in space emerges as an entropic force between species. Here, we use this concept of entropy to understand the underlying physics behind the formation of attractive and repulsive forces by imagining that space is filled with free Brownian degrees of freedom. We incorporate the radius of bodies and the distance between them into entropic force relation systematically. Using this modified gravitational entropic force, we derive the attractive entropic force between bodies without considering their spin. We further hypothesize a possible mechanism for the formation of the repulsive force between two bodies. We visually elaborate that the repulsive entropic force will be manifested through the rotation of degrees of freedom around the spinning particles.

Keywords: entropy, information, force, Brownian Motions

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Authors: Sachinkumar Patil, Sonali Patil, Shitalkumar Patil

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Nanoparticles played important role in the biomedicine. New advanced methods having great potential apllication in the diagnosis and therapy of cancer. Now a day’s magnetic nanoparticles used in cancer therapy. Cancer is the major disease causes death. Magnetic nanoparticles show response to the magnetic field on the basis of this property they are used in cancer therapy. Cancer treated with hyperthermia by using magnetic nanoparticles it is unconventional but more safe and effective method. Magnetic nanoparticles prepared by using different innovative techniques that makes particles in uniform size and desired effect. Magnetic nanoparticles already used as contrast media in magnetic resonance imaging. A magnetic nanoparticle has been great potential application in cancer diagnosis and treatment as well as in gene therapy. In this review we will discuss the progress in cancer therapy based on magnetic nanoparticles, mainly including magnetic hyperthermia, synthesis and characterization of magnetic nanoparticles, mechanism of magnetic nanoparticles and application of magnetic nanoparticles.

Keywords: magnetic nanoparticles, synthesis, characterization, cancer therapy, hyperthermia, application

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Authors: P. Mounnarath, U. Schmitz, Ch. Zhang

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Fragility analysis is an effective tool for the seismic vulnerability assessment of civil structures in the last several years. The design of the expansion joints according to various bridge design codes is almost inconsistent, and only a few studies have focused on this problem so far. In this study, the influence of the expansion joint clearances between the girder ends and the abutment backwalls on the seismic fragility assessment of continuous integral bridge frames is investigated. The gaps (ranging from 60 mm, 150 mm, 250 mm and 350 mm) are designed by following two different bridge design code specifications, namely, Caltrans and Eurocode 8-2. Five bridge models are analyzed and compared. The first bridge model serves as a reference. This model uses three-dimensional reinforced concrete fiber beam-column elements with simplified supports at both ends of the girder. The other four models also employ reinforced concrete fiber beam-column elements but include the abutment backfill stiffness and four different gap values. The nonlinear time history analysis is performed. The artificial ground motion sets, which have the peak ground accelerations (PGAs) ranging from 0.1 g to 1.0 g with an increment of 0.05 g, are taken as input. The soil-structure interaction and the P-Δ effects are also included in the analysis. The component fragility curves in terms of the curvature ductility demand to the capacity ratio of the piers and the displacement demand to the capacity ratio of the abutment sliding bearings are established and compared. The system fragility curves are then obtained by combining the component fragility curves. Our results show that in the component fragility analysis, the reference bridge model exhibits a severe vulnerability compared to that of other sophisticated bridge models for all damage states. In the system fragility analysis, the reference curves illustrate a smaller damage probability in the earlier PGA ranges for the first three damage states, they then show a higher fragility compared to other curves in the larger PGA levels. In the fourth damage state, the reference curve has the smallest vulnerability. In both the component and the system fragility analysis, the same trend is found that the bridge models with smaller clearances exhibit a smaller fragility compared to that with larger openings. However, the bridge model with a maximum clearance still induces a minimum pounding force effect.

Keywords: expansion joint clearance, fiber beam-column element, fragility assessment, time history analysis

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Authors: Adam Janásek, Marek Pagáč

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The article is looking for an experimental determination of tool life tests for ceramic cutting inserts. Mentioned experimental determination should provide an added information about cutting process. The mechanism of tool wear, cutting temperature in machining, quality machined surface and machining process itself is the information, which are important for whole manufacturing process. Mainly, the roughness plays very important role in determining how a real object will interact with its environment. The main aim was to determine the number of machined inserts, tool life and micro-geometry, as well. On the basis of previous tests the tool-wear was measured at constant cutting parameter which is more typical for high volume manufacturing processes.

Keywords: ceramic, insert, machining, surface roughness, tool-life, tool-wear

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Authors: Lincy Stephen, N. Yogesh, G. Vasantharajan, V. Subramanian

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This paper presents the design and simulation of a five band metamaterial absorber at microwave frequencies. The absorber unit cell consists of squares and strips arranged as the top layer and a metallic ground plane as the bottom layer on a dielectric substrate. Simulation results show five near perfect absorption bands at 3.15 GHz, 7.15 GHz, 11.12 GHz, 13.87 GHz, and 16.85 GHz with absorption magnitudes 99.68%, 99.05%, 96.98%, 98.36% and 99.44% respectively. Further, the proposed absorber exhibits polarization insensitivity and wide angle receptivity. The surface current analysis is presented to explain the mechanism of absorption in the structure. With these preferable features, the proposed absorber can be excellent choice for potential applications such as electromagnetic interference (EMI) shielding, radar cross section reduction.

Keywords: electromagnetic absorber, metamaterial, multi- band, polarization insensitive, wide angle receptive

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Authors: Wang Zhenzhen, Wang Xu, Hong Liangping

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With the rapid development of cities, the way that people commute has changed greatly, meanwhile, people turn to require more on physical and psychological aspects in the contemporary world. However, the current urban road landscape ignores these changes, for example, those road landscape elements are boring, confusing, fragmented and lack of integrity and hierarchy. Under such current situation, in order to shape beautiful, identifiable and unique road landscape, this article concentrates on the target of imaginability. This paper analyses the main elements of the urban road landscape, the concept of image and its generation mechanism, and then discusses the necessity and connotation of building imaginable urban road landscape as well as the main problems existing in current urban road landscape in terms of imaginability. Finally, this paper proposes how to design imaginable urban road landscape in details based on a specific case.

Keywords: identifiability, imaginability, road landscape, the image of the city

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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

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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

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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

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Authors: R. Frikha, H. Kamoun

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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

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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

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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

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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

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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

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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 (T_o). 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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Authors: John G. Skelly, Peter K. Dearden, Thomas W. R. Harrop, Sarah N. Inwood, Joseph Guhlin

Abstract:

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 154

Authors: Nigar Kantarci Carsibasi

Abstract:

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 128