Search results for: pan drug resistance

Authors: Akbar Esmaeili, Zahra Salarieh

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Cerium oxide nanoparticles (nano-series) are used as catalysts in industrial applications due to their free radical scavenging properties. Given that free radicals play an essential role in the pathology of many neurological diseases, we investigated the use of nanocrystals as a potential therapeutic agent for oxidative damage. This project synthesized nano-series from a new and environmentally friendly bio-pathway. Investigation of cerium nitrate in culture medium containing inoculated Lactobacillus acidophilus strain before incubation produces nano-series. Loaded with glatiramer acetate (GA) was formed by coating carboxymethylcellulose (CMC) and CeO2. FE-SEM analysis showed nano-series in the 9-11 nm range, spherical shape, and uniform particle size distribution. Cubic nanoparticles containing anti-multiple sclerosis (anti-Ms) treatment called GA were used. Glycerol monostearate (GMS) was used as a fat base, and evening primrose extract was used as an anti-inflammatory in cubosomes. Design-Expert® software was used to study the effects of different formulation factors on the properties of GAloaded cubic dispersions. Thirty GA-labeled cubic dispersions were prepared with GA-labeled carboxymethylcellulose and evaluated in vitro. The results showed an average nano-series size of 89.02 and a zeta potential of -49.9. Cubosomes containing GA-CMC/CeO2 showed a stable release profile for 180 min. The results showed that cubosomes containing GA-CMC/CeO2 could be a promising drug carrier with normal release behavior.

Keywords: ciochemistry, biotechnology, molecular, biology

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Authors: Yasser A. Khalifa, Michael J. Tait, A. M. Asce, Wael W. El-Dakhakhni, M. Asce

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The quasi-static resistance functions for orthogonal corrugated core sandwich panels were determined experimentally. According to the American and Canadian codes for blast resistant designs of buildings UFC 3-340-02, ASCE/SEI 59-11, and CSA/ S850-12 the dynamic behavior is related to the static behavior under uniform loading. The target was to design a lightweight, relatively cheap, and quick sandwich panel to be employed as a sacrificial cladding for important buildings. For that an available corrugated cold formed steel sheet profile in North America was used as a core for the sandwich panel, in addition to using a quick, relatively low cost fabrication technique in the construction process. Six orthogonal corrugated core sandwich panels were tested and the influence of core sheet gauge on the behavior of the sandwich panels was explored using two different gauges. Failure modes, yield forces, ultimate forces, and corresponding deformations were determined and discussed.

Keywords: cold formed steel, lightweight structure, sandwich panel, sacrificial cladding, uniform loading

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Authors: Kevser Dincer, Basma Waisi, M. Ozan Ozdemir, Ugur Pasaogullari, Jeffrey McCutcheon

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Nanofibers are defined as fibers with diameters less than 100 nanometers. They can be produced by interfacial polymerization, electrospinning and electrostatic spinning. In this study, behaviours of activated carbon nano fiber (ACNF), carbon nano-fiber (CNF), Polyacrylonitrile/carbon nanotube (PAN/CNT), Polyvinyl alcohol/nano silver (PVA/Ag) in PEM fuel cells are investigated experimentally. This material was used as gas diffusion layer (GDL) in PEM fuel cells. When the performances of these cells are compared to each other at 5x5 cm2 cell, it is found that the PVA/Ag exhibits the best performance among all. In this work, nano fiber and nano fiber/nano particles electrical conductivities have been studied to understand their effects on PEM fuel cell performance. According to the experimental results, the maximum electrical conductivity performance of the fuel cell with nanofiber was found to be at PVA/Ag. The electrical conductivities of CNF, ACNF, PAN/CNT are lower for PEM. The resistance of cell with PVA/Ag is lower than the resistance of cell with PAN/CNT, ACNF, CNF.

Keywords: proton exchange membrane fuel cells, electrospinning, carbon nano fiber, activate carbon nano-fiber, PVA fiber, PAN fiber, carbon nanotube, nano particle nanocomposites

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Authors: Mazouzi Nourdjihane, K. Boutemak, A. Haddad, Y. Chegreouche

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In the last decades, biodegradable polymers have been considered as one of the most popular options for the delivery of drugs and various conventional doses. The film forming system (FFS) can be used in topical, transdermal, ophthalmic, oral and gastric applications. Recently this system has focused on improving drug delivery, which can promote drug release. In this context, the aim of this study is to create polymeric film-forming systems for the stomach and to evaluate and test their gastroprotective effects, comparing the effects of changes in composition on film characteristics. It uses a plant-derived polyphenol extract extracted from fennel to demonstrate anti-inflammatory activity in the film. The films are made from hydroxypropyl methylcellulose polymer and different types of plastic, glycerol and polyethylene glycol. The ffs properties show that MgO-glycerol-reinforced hydroxypropylmethylcellulose (HPMC-MgO-Gly) is better than that based on MgO-PEG-reinforced hydroxypropylmethylcellulose (HPMC-MgO-PEG). It is durable, has a faster drying time and allows for maximum recovery. Water vapor strength and blowing speed and other additions show another advantage of HPMC-MgO-Gly compared to HPMC-MgO-PEG, indicating good adhesion between the support (top) and film production. In this study, the gastroprotective effect of fennel phenol extract was found, showing that this plant material has a gastroprotective effect on ulcers and that the film can absorb the active substance.

Keywords: film formin system, hydroxypropyl methylcellulose, magnesium oxide, in vivo

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Authors: Mohammad Faheem, M. Tabish Rehman, Mohd Danishuddin, Asad U. Khan

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The worldwide dissemination of CTX-M type β-lactamases is a threat to human health. Previously, we have reported the spread of blaCTX-M-15 gene in different clinical strains of Enterobacteriaceae from the hospital settings of Aligarh in north India. In view of the varying resistance pattern against cephalosporins and other β-lactam antibiotics, we intended to understand the correlation between MICs and catalytic activity of CTX-M-15. In this study, steady-state kinetic parameters and MICs were determined on E. coli DH5α transformed with blaCTX-M-15 gene that was cloned from Enterobacter cloacae (EC-15) strain of clinical background. The effect of conventional β-lactamase inhibitors (clavulanic acid, sulbactam and tazobactam) on CTX-M-15 was also studied. We have found that tazobactam is the best among these inhibitors against CTX-M-15. The inhibition characteristic of tazobactam is defined by its very low IC50 value (6 nM), high affinity (Ki = 0.017 µM) and better acylation efficiency (k+2/K9 = 0.44 µM-1s-1). It forms an acyl-enzyme covalent complex, which is quite stable (k+3 = 0.0057 s-1). Since increasing resistance has been reported against conventional b-lactam antibiotic-inhibitor combinations, we aspire to design a non-b-lactam core containing b-lactamase inhibitor. For this, we screened ZINC database and performed molecular docking to identify a potential non-β-lactam based inhibitor (ZINC03787097). The MICs of cephalosporin antibiotics in combination with this inhibitor gave promising results. Steady-state kinetics and molecular docking studies showed that ZINC03787097 is a reversible inhibitor which binds non-covalently to the active site of the enzyme through hydrogen bonds and hydrophobic interactions. Though, it’s IC50 (180 nM) is much higher than tazobactam, it has good affinity for CTX-M-15 (Ki = 0.388 µM). This study concludes that ZINC03787097 compound can be used as seed molecule to design more efficient non-b-lactam containing b-lactamase inhibitor that could evade pre-existing bacterial resistance mechanisms.

Keywords: ESBL, non-b-lactam-b-lactamase inhibitor, bioinformatics, biomedicine

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Authors: Yousef M. Abouzeed A. Elfahem, F. Zgheel, M. A. Saad, Mohamed O. Ahmed

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The bioactive properties of phytochemicals indicate their potential as natural drug products to prevent and treat human disease; in particular, compounds with antioxidant and antimicrobial activities may represent a novel class of safe and effective drugs. Following desiccation, grapes (Vitis vinifera) become more resistant to microbial-based degradation, suggesting that raisins may be a source of antimicrobial compounds. To investigate this hypothesis, total phenolic extracts were obtained from common raisins, local market-sourced. The acetone extract was tested for antibacterial activity against four prevalent bacterial pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella spp. and Escherichia coli). Antibiotic sensitivity and the Minimum Inhibitory Concentration (MIC) were determined for each bacterium. High performance liquid chromatography was used to identify compounds in the total phenolic extract. The raisin phenolic extract inhibited growth of all the tested bacteria; the greatest inhibitive effect (normalized to cefotaxime sodium control antibiotic) occurred against P. aeruginosa, followed by S. aureus > Salmonella spp.= E. coli. The phenolic extracts contained the bioactive compounds catechin, quercetin, and rutin. Thus, phytochemicals in raisin extract have antibacterial properties; this plant-based extract, or its bioactive constituents, may represent a promising natural preservative or antimicrobial agent for the food industry or anti-infective drug.

Keywords: Vitis vinifera raisin, extraction, phenolic compounds, antibacterial activity

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Authors: Kuate Tueguem William Norbert, Ngoh Dooh Jules Patrice, Kone Sangou Abdou Nourou, Mboussi Serge Bertrand, Chewachang Godwill Mih, Essome Sale Charles, Djuissi Tohoto Doriane, Ambang Zachee

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The objectives of this study were to evaluate the effects of foliar application of 24-epibrassinolide (EBR) on the development of rice helminthosporiosis caused by Bipolaris oryzae and its influence on the improvement of growth parameters and induction of the synthesis of defense substances in the rice plants. The experimental asset up involved a multifactorial split-plot with two varieties (NERICA 3 and local variety KAMKOU) and five treatments (T0: control, T1: EBR, T2: BANKO PLUS (fungicide), T3: NPK (chemical fertilizer), T4: mixture: NPK + BANKO PLUS + EBR) with three repetitions. Agro-morphological and epidemiological parameters, as well as substances for plant resistance, were evaluated over two growing seasons. The application of the EBR induced significant growth of the rice plants for the 2015 and 2016 growing seasons on the two varieties tested compared to the T0 treatment. At 74 days after sowing (DAS), NERICA 3 showed plant heights of 58.9 ± 5.4; 83.1 ± 10.4; 86.01 ± 9.4; 69.4 ± 11.1 and 87.12 ± 7.4 cm at T0; T1; T2; T3, and T4, respectively. Plant height for the variety KAMKOU varied from 87,12 ± 8,1; 88.1 ± 8.1 and 92.02 ± 6.3 cm in T1, T2, and T3 to 74.1 ± 8.6 and 74.21 ± 11.4 cm in T0 and T3. In accordance with the low rate of expansion of helminthosporiosis in experimental plots, EBR (T1) significantly reduced the development of the disease with severities of 0.0; 1.29, and 2.04%, respectively at 78; 92, and 111 DAS on the variety NERICA 3 compared with1; 3.15 and 3.79% in the control T0. The reduction of disease development/severity as a result of the application of EBR is due to the induction of acquired resistance of rice varieties through increased phenol (13.73 eqAG/mg/PMF) and total protein (117.89 eqBSA/mg/PMF) in the T1 treatment against 5.37 eqAG/mg/PMF and 104.97 eqBSA/mg/PMF in T0 for the NERICA 3 variety. Similarly, on the KAMKOU variety, 148.53 eqBSA/mg/PMF were protein and 6.10 eqAG/mg/PMF of phenol in T1. In summary, the results show the significant effect of EBR on plant growth, yield, synthesis of secondary metabolites and defense proteins, and disease resistance. The EBR significantly reduced losses of rice grains by causing an average gain of about 1.55 t/ha compared to the control and 1.00 t/ha compared to the NPK-based treatment for the two varieties studied. Further, the enzymatic activities of PPOs, POXs, and PR2s were higher in leaves from treated EBR-based plants. These results show that 24-epibrassinolide can be used in the control of helminthosporiosis of rice to reduce disease and increase yields.

Keywords: Oryza sativa, 24-epibrassinolide, helminthosporiosis, secondary metabolites, PR proteins, acquired resistance

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Authors: Abhijit Trailokya, Kamlesh Patel

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Background: Hypertension is a common disease seen in clinical practice and is associated with high morbidity and mortality. Many patients require combination therapy for the management of hypertension. Objective: To evaluate co-morbidities, risk factors and management practices of hypertension in Indian population. Material and methods: A total of 1596 hypertensive adult patients received anti-hypertensive medications were studied in a cross-sectional, multi-centric, non-interventional, observational registry. Statistical analysis: Categories or nominal data was expressed as numbers with percentages. Continuous variables were analyzed by descriptive statistics using mean, SD, and range Chi square test was used for in between group comparison. Results: The study included 73.50% males and 26.50% females. Overweight (50.50%) and obesity (30.01%) was common in the hypertensive patients (n=903). A total of 54.76% patients had history of smoking. Alcohol use (33.08%), sedentary life style (32.96%) and history of tobacco chewing (17.92%) were the other lifestyle habits of hypertensive patients. Diabetes (36.03%) and dyslipidemia (39.79%) history was common in these patients. Family history of hypertension and diabetes was seen in 82.21% and 45.99% patients respectively. Most (89.16%) patients were treated with combination of antihypertensive agents. ARBs were the by far most commonly used agents (91.98%) followed by calcium channel blockers (68.23%) and diuretics (60.21%). ARB was the most (80.35%) preferred agent as monotherapy. ARB was also the most common agent as a component of dual therapy, four drug and five drug combinations. Conclusion: Most of the hypertensive patients need combination treatment with antihypertensive agents. ARBs are the most preferred agents as monotherapy for the management of hypertension. ARBs are also very commonly used as a component of combination therapy during hypertension management.

Keywords: antihypertensive, hypertension, management, ARB

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Authors: J. Roberto Lopez, Hened Saade, Graciela Morales, Javier Enriquez, Raul G. Lopez

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Implementation of systems based on nanostructures for drug delivery applications have taken relevance in recent studies focused on biomedical applications. Although there are several nanostructures as drugs carriers, the use of polymeric nanoparticles (PNP) has been widely studied for this purpose, however, the main issue for these nanostructures is the size control below 50 nm with a narrow distribution size, due to they must go through different physiological barriers and avoid to be filtered by kidneys (< 10 nm) or the spleen (> 100 nm). Thus, considering these and other factors, it can be mentioned that drug-loaded nanostructures with sizes varying between 10 and 50 nm are preferred in the development and study of PNP/drugs systems. In this sense, the Semicontinuous Heterophase Polymerization (SHP) offers the possibility to obtain PNP in the desired size range. Considering the above explained, methacrylic copolymer nanoparticles were obtained under SHP. The reactions were carried out in a jacketed glass reactor with the required quantities of water, ammonium persulfate as initiator, sodium dodecyl sulfate/sodium dioctyl sulfosuccinate as surfactants, methyl methacrylate and methacrylic acid as monomers with molar ratio of 2/1, respectively. The monomer solution was dosed dropwise during reaction at 70 °C with a mechanical stirring of 650 rpm. Nanoparticles of poly(methyl methacrylate-co-methacrylic acid) were loaded with acetylsalicylic acid (ASA, aspirin) by a chemical adsorption technique. The purified latex was put in contact with a solution of ASA in dichloromethane (DCM) at 0.1, 0.2, 0.4 or 0.6 wt-%, at 35°C during 12 hours. According to the boiling point of DCM, as well as DCM and water densities, the loading process is completed when the whole DCM is evaporated. The hydrodynamic diameter was measured after polymerization by quasi-elastic light scattering and transmission electron microscopy, before and after loading procedures with ASA. The quantitative and qualitative analyses of PNP loaded with ASA were measured by infrared spectroscopy, differential scattering calorimetry and thermogravimetric analysis. Also, the molar mass distributions of polymers were determined in a gel permeation chromatograph apparatus. The load capacity and efficiency were determined by gravimetric analysis. The hydrodynamic diameter results for methacrylic PNP without ASA showed a narrow distribution with an average particle size around 10 nm and a composition methyl methacrylate/methacrylic acid molar ratio equal to 2/1, same composition of Eudragit S100, which is a commercial compound widely used as excipient. Moreover, the latex was stabilized in a relative high solids content (around 11 %), a monomer conversion almost 95 % and a number molecular weight around 400 Kg/mol. The average particle size in the PNP/aspirin systems fluctuated between 18 and 24 nm depending on the initial percentage of aspirin in the loading process, being the drug content as high as 24 % with an efficiency loading of 36 %. These average sizes results have not been reported in the literature, thus, the methacrylic nanoparticles here reported are capable to be loaded with a considerable amount of ASA and be used as a drug carrier.

Keywords: aspirin, biocompatibility, biodegradable, Eudragit S100, methacrylic nanoparticles

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Authors: Seyed Abolhassan Naeini, Hamed Yekehdehghan

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One of the factors that affect the constructions adjacent to a slope is stability. There are various methods for the stability of the slopes, one of which is the use of concrete group piles. This study, using FLAC3D software, has tried to investigate the changes in safety coefficient because of the use of concrete group piles. In this research, furthermore, the optimal position of the piles has been investigated and the results show that the group pile does not affect the toe of the slope. In addition, the effect of the piles' burial depth on the slope has been studied. Results show that by increasing the piles burial depth on a slope, the level of stability and as a result the safety coefficient increases. In the investigation of reducing the distance between the piles and increasing the depth of underground water, it was observed that the obtained safety coefficient increased. Finally, the effect of the resistance of the lower stabilizing layer of the slope on stabilization was investigated by the pile group. The results showed that due to the behavior of the pile as a deep foundation, the stronger the soil layers are in the stable part of a stronger slope (in terms of resistance parameters), the more influential the piles are in enhancing the coefficient of safety.

Keywords: safety coefficient, group pile, slope, stability, FLAC3D software

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Authors: M. Towhidur Rahman, Nasim Zaman Piyas, M. Sadiqul Baree, Shahnewaz Ahmed

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The design of high-speed craft has recently become one of the most active areas of naval architecture. Speed increase makes these vehicles more efficient and useful for military, economic or leisure purpose. The planing hull is designed specifically to achieve relatively high speed on the surface of the water. Speed on the water surface is closely related to the size of the vessel and the installed power. The Savitsky method was first presented in 1964 for application to non-monohedric hulls and for application to stepped hulls. This method is well known as a reliable comparative to CFD analysis of hull resistance. A computer program based on Savitsky’s method has been developed using MATLAB. The power of high-speed vessels has been computed in this research. At first, the program reads some principal parameters such as displacement, LCG, Speed, Deadrise angle, inclination of thrust line with respect to keel line etc. and calculates the resistance of the hull using empirical planning equations of Savitsky. However, some functions used in the empirical equations are available only in the graphical form, which is not suitable for the automatic computation. We use digital plotting system to extract data from nomogram. As a result, value of wetted length-beam ratio and trim angle can be determined directly from the input of initial variables, which makes the power calculation automated without manually plotting of secondary variables such as p/b and other coefficients and the regression equations of those functions are derived by using data from different charts. Finally, the trim angle, mean wetted length-beam ratio, frictional coefficient, resistance, and power are computed and compared with the results of Savitsky and good agreement has been observed.

Keywords: nomogram, planing hull, principal parameters, regression

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Authors: P. Gao, Z. Q. Li, Y. G. Jin

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In the past 10 years, computers and cellphones have become one of the most important factors in our lives, and one which has a tremendously negative impact on our muscles. Muscle tension may be one of the causes of sleep disturbance. Tension in the shoulders and neck can affect blood circulation to the muscles. This research uses a dry needling treatment to reduce muscle tension in order to determine if the strain in the head and shoulders can influence sleep duration. All 38 patients taking part in the testing suffered from tinnitus and have been experiencing disturbed sleep for at least one to five years. Even after undergoing drug therapy treatments and traditional acupuncture therapies, their sleep disturbances have not shown any improvement. After five to 10 dry needling treatments, 24 of the patients reported an improvement in their sleep duration. Five patients considered themselves to be completely recovered, while 12 patients experienced no improvement. This study investigated these pathogenic and therapeutic problems. The standard treatment for sleep disturbances is drug-based therapy; the results of most standard treatments are unfortunately negative. The result of this clinical research has demonstrated that: The possible cause of sleep disturbance for a lot of patients is the result of tensions in the neck and shoulder muscles. Blood circulation to those muscles is also influenced by the duration of sleep. Hypertonic neck and shoulder muscles are considered to impact sleeping patterns and lead to disturbed sleep. Poor posture, often adopted while speaking on the phone, is one of the main causes of hypertonic neck and shoulder muscle problems. The dry needling treatment specifically focuses on the release of muscle tension.

Keywords: dry needling, muscle tension, sleep duration, hypertonic muscles

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Authors: Hannah S. Elizabeth, D. Gnanasekaran, M. R. Manju Gowda, Antony George

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Phytoremediation a new technology of remediating the contaminated soil, water and air using plants and serves as a green technology with environmental friendly approach. The main aim of this technique is cleansing and detoxifying of organic compounds, organo-phosphorous pesticides, heavy metals like arsenic, iron, cadmium, gold, radioactive elements which cause teratogenic and life threatening diseases to mankind and animal kingdom when consume the food crops, vegetables, fruits, cerals, and millets obtained from the contaminated soil. Also, directly they may damage the genetic materials thereby alters the biosynthetic pathways of secondary metabolites and other phytoconstituents which may have different pharmacological activities which lead to lost their efficacy and potency as well. It would reflect in mutagenicity, drug resistance and affect other antagonistic properties of normal metabolism. Is the technology for real clean-up of contaminated soils and the contaminants which are potentially toxic. It reduces the risks produced by a contaminated soil by decreasing contaminants using plants as a source. The advantages are cost-effectiveness and less ecosystem disruption. Plants may also help to stabilize contaminants by accumulating and precipitating toxic trace elements in the roots. Organic pollutants can potentially be chemically degraded and ultimately mineralized into harmless biological compounds. Hence, the use of plants to revitalize contaminated sites is gaining more attention and preferred for its cost-effective when compared to other chemical methods. The introduction of harmful substances into the environment has been shown to have many adverse effects on human health, agricultural productivity, and natural ecosystems. Because the costs of growing a crop are minimal compared to those of soil removal and replacement, the use of plants to remediate hazardous soils is seen as having great promise.

Keywords: cost effective, eco-friendly, phytoremediation, secondary metabolites

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Authors: Hamdi Amroun, Yacine Benziani, Mehdi Ammi

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In this paper, we want to determine whether the accurate prediction of nicotine concentration can be obtained by using a network of smart objects and an e-cigarette. The approach consists of, first, the recognition of factors influencing smoking cessation such as physical activity recognition and participant’s behaviors (using both smartphone and smartwatch), then the prediction of the configuration of the e-cigarette (in terms of nicotine concentration, power, and resistance of e-cigarette). The study uses a network of commonly connected objects; a smartwatch, a smartphone, and an e-cigarette transported by the participants during an uncontrolled experiment. The data obtained from sensors carried in the three devices were trained by a Long short-term memory algorithm (LSTM). Results show that our LSTM-based model allows predicting the configuration of the e-cigarette in terms of nicotine concentration, power, and resistance with a root mean square error percentage of 12.9%, 9.15%, and 11.84%, respectively. This study can help to better control consumption of nicotine and offer an intelligent configuration of the e-cigarette to users.

Keywords: Iot, activity recognition, automatic classification, unconstrained environment

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Authors: Harjot Singh Gill, Neelkanth Grover, Jwala Parshad Singla

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The main aim of this research work is to present the effect of coating on two different grades of grey cast iron using detonation spray method. Ni20Cr and Al2O3-13TiO2 powders were sprayed using detonation gun onto GI250 and GIHC substrates and the results as well as coating surface morphology of the coating is studied by XRD and SEM/EDAX analysis. The wear resistance of Ni20Cr and Al2O3-13TiO2 has been investigated on pin-on-disc tribometer using ASTM G99 standards. Cumulative wear rate and coefficient of friction (µ) were calculated under three normal load of 30N, 40N, 50N at constant sliding velocity of 1m/s. Worn out surfaces were analyzed by SEM/EDAX. The results show significant resistance to wear with Al2O3-13TiO2 coating as compared to Ni20Cr and bare substrates. SEM/EDAX analysis and cumulative wear loss bar charts clearly explain the wear behavior of coated as well as bare sample of GI250 and GIHC.

Keywords: detonation spray, grey cast iron, wear rate, coefficient of friction

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Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

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Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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Authors: Asma'u Mahe, Abdullahi A. Imam, Adamu J. Alhassan, Nasiru Abdullahi, Sadiya A. Bichi, Nura Lawal, Kamaluddeen Babagana

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Malaria is a disease with global health significance. It is caused by parasites and transmitted by Anopheles mosquitoes. Increase in insecticide resistance threatens the disease vector control. The strength of selection pressure acting on a mosquito population in relation to insecticide resistance can be assess by determining the genetic diversity of a fragment spanning exon- 20 of IIS6 of the voltage gated sodium channel (VGSC). Larval samples reared to adulthood were identified and kdr (knock down resistance) profile was determined. The DNA sequences were used to assess the patterns of genetic differentiation by determining the levels of genetic variability between the Anopheles mosquitoes. Genetic differentiation of the Anopheles mosquitoes based on a portion of the voltage gated sodium channel gene was obtained. Polymorphisms were detected; sequence variation and analysis were presented as a phylogenetic tree. Phylogenetic tree of VGSC haplotypes was constructed for samples of the Anopheles mosquitoes using the maximum likelihood method in MEGA 6.0 software. DNA sequences were edited using BioEdit sequence editor. The edited sequences were aligned with reference sequence (Kisumu strain). Analyses were performed as contained in dnaSP 5.10. Results of genetic parameters of polymorphism and haplotype reconstruction were presented in count. Twenty sequences were used for the analysis. Regions selected were 1- 576, invariable (monomorphic) sites were 460 while variable (polymorphic) sites were 5 giving the number of total mutations observed in this study. Mutations obtained from the study were at codon 105: TTC- Phenylalanine replaces TCC- Serine, codon 513: TAG- Termination replaces TTG- Leucine, codon 153, 300 and 553 mutations were non-synonymous. From the constructed phylogenetic tree, some groups were shown to be closer with Exon20Gambiae Kisumu (Reference strain) having some genetic distance, while 5-Exon20Gambiae-F I13.ab1, 18-Exon20Gambiae-F C17.ab1, and 2-Exon20Gambiae-F C13.ab1 clustered together genetically differentiated away from others. Mutations observed in this study can be attributed to the high insecticide resistance profile recorded in the study areas. Haplotype networks of pattern of genetic variability and polymorphism for the fragment of the VGSC sequences of sampled Anopheles mosquitoes revealed low haplotypes for the present study. Haplotypes are set of closely linked DNA variation on X-chromosome. Haplotypes were scaled accordingly to reflect their respective frequencies. Low haplotype number, four VGSC-1014F haplotypes were observed in this study. A positive association was previously established between low haplotype number of VGSC diversity and pyrethroid resistance through kdr mechanism. Significant values at (P < 0.05) of Tajima D and Fu and Li D’ were observed for some of the results indicating possible signature of positive selection on the fragment of VGSC in the study. This is the first report of VGSC-1014F in the study site. Based on the results, the mutation was present in low frequencies. However, the roles played by the observed mutations need further investigation. Mutations, environmental factors among others can affect genetic diversity. The study area has recorded increase in insecticide resistance that can affect vector control in the area. This finding might affect the efforts made against malaria. Sequences were deposited in GenBank for Accession Number.

Keywords: anopheles mosquitoes, insecticide resistance, kdr, malaria, voltage gated sodium channel

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Authors: Neusa Fernanda Torres, Buyisile Chibi, Lyn E. Middleton, Vernon P. Solomon, Tivani P. Mashamba-Thompson

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Background: Self-medication with antibiotics (SMA) is a global concern, with a higher incidence in low and middle-income countries (LMICs). Despite intense world-wide efforts to control and promote the rational use of antibiotics, continuing practices of SMA systematically exposes individuals and communities to the risk of antibiotic resistance and other undesirable antibiotic side effects. Moreover, it increases the health systems costs of acquiring more powerful antibiotics to treat the resistant infection. This review thus maps evidence on the factors influencing self-medication with antibiotics in these settings. Methods: The search strategy for this review involved electronic databases including PubMed, Web of Knowledge, Science Direct, EBSCOhost (PubMed, CINAHL with Full Text, Health Source - Consumer Edition, MEDLINE), Google Scholar, BioMed Central and World Health Organization library, using the search terms:’ Self-Medication’, ‘antibiotics’, ‘factors’ and ‘reasons’. Our search included studies published from 2007 to 2017. Thematic analysis was performed to identify the patterns of evidence on SMA in LMICs. The mixed method quality appraisal tool (MMAT) version 2011 was employed to assess the quality of the included primary studies. Results: Fifteen studies met the inclusion criteria. Studies included population from the rural (46,4%), urban (33,6%) and combined (20%) settings, of the following LMICs: Guatemala (2 studies), India (2), Indonesia (2), Kenya (1), Laos (1), Nepal (1), Nigeria (2), Pakistan (2), Sri Lanka (1), and Yemen (1). The total sample size of all 15 included studies was 7676 participants. The findings of the review show a high prevalence of SMA ranging from 8,1% to 93%. Accessibility, affordability, conditions of health facilities (long waiting, quality of services and workers) as long well as poor health-seeking behavior and lack of information are factors that influence SMA in LMICs. Antibiotics such as amoxicillin, metronidazole, amoxicillin/clavulanic, ampicillin, ciprofloxacin, azithromycin, penicillin, and tetracycline, were the most frequently used for SMA. The major sources of antibiotics included pharmacies, drug stores, leftover drugs, family/friends and old prescription. Sore throat, common cold, cough with mucus, headache, toothache, flu-like symptoms, pain relief, fever, running nose, toothache, upper respiratory tract infections, urinary symptoms, urinary tract infection were the common disease symptoms managed with SMA. Conclusion: Although the information on factors influencing SMA in LMICs is unevenly distributed, the available information revealed the existence of research evidence on antibiotic self-medication in some countries of LMICs. SMA practices are influenced by social-cultural determinants of health and frequently associated with poor dispensing and prescribing practices, deficient health-seeking behavior and consequently with inappropriate drug use. Therefore, there is still a need to conduct further studies (qualitative, quantitative and randomized control trial) on factors and reasons for SMA to correctly address the public health problem in LMICs.

Keywords: antibiotics, factors, reasons, self-medication, low and middle-income countries (LMICs)

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Authors: Maryam Monazzah, Ronak Samadpour, Mehdi Nasr-esfahani, Fatemeh Qalavand, Marziye Motamedi

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Bipolaris sorokiniana, and Heterodera filipjevi, are important wheat diseases that lead to yield losses worldwide. Identifying novel resistant sources helps us combat these devastating diseases. In this study, we studied the role of Cre3 gene and antioxidant enzymes in the immune responses of wheat genotypes to H. filipjevi and B. sorokiniana. Therefore, real-time PCR analysis using Cre3 gene marker, a resistant gene to cereal cyst nematodes, was conducted on leaves and roots, along with changes ‎in the activity of antioxidant enzymes, peroxidase, and catalase. Enzyme activity assay was performed on roots attacked by nematode and in leaves infected with Bipolaris. Wheat accessions including “Bam” (resistant), “Parsi” (moderately-resistant), “Azar2”, “Ohadi”, “Homa” (highly-susceptible) were previously screened against both stresses under greenhouse and field conditions. Results showed that Cre3 expression against cyst nematodes was significantly higher in resistant cultivars compared to susceptible cultivars. Cre3 was used in marker-assisted selection programs to identify genotypes carrying resistant genes to cyst nematodes. Interestingly, Cre3 was also up-regulated in both tissues of resistant cultivars to B. sorokiniana. Therefore, Cre3 in wheat similarly modulates immunity against B. sorokiniana and might be one of the central components of the induced immune system in wheat. The activity of antioxidant enzymes also indicated the highest increase in resistant genotypes upon both stresses that subsequently neutralize oxidative stress in tissues and decrease damage. Further studies on these resistance components may help us gain insight into the molecular basis of resistance and shed new light on the interaction and overlap between different forms of stress.

Keywords: Bipolaris sorokiniana, Heterodera filipjevi, resistant gene expression, wheat

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Authors: R. P. Hewawasam, M. H. A. D. de Silva, M. A. G. Iresha

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Obesity is associated with an increased risk of developing insulin resistance. Insulin resistance often progresses to type-2 diabetes mellitus and is linked to a wide variety of other pathophysiological features including hypertension, hyperlipidemia, atherosclerosis (metabolic syndrome) and polycystic ovarian syndrome. Macrosomia is common in infants born to not only women with gestational diabetes mellitus but also non-diabetic obese women. During the past two decades, obesity in children and adolescents has risen significantly in Asian populations including Sri Lanka. There is increasing evidence to believe that infants who are born large for gestational age (LGA) are more likely to be obese in childhood. It is also established from previous studies that Asian populations have higher percentage body fat at a lower body mass index compared to Caucasians. High leptin levels in cord blood have been reported to correlate with fetal adiposity at birth. Previous studies have also shown that cord blood C-peptide and insulin levels are significantly and positively correlated with birth weight. Therefore, the objective of this preliminary study was to determine the relationship between parameters of fetal insulin resistance such as leptin, C-peptide and insulin and the birth weight of the newborn in a study population in Southern Sri Lanka. Umbilical cord blood was collected from 90 newborns and the concentration of insulin, leptin, and C-peptide were measured by ELISA technique. Birth weight, length, occipital frontal, chest, hip and calf circumferences of newborns were measured and characteristics of the mother such as age, height, weight before pregnancy and weight gain were collected. The relationship between insulin, leptin, C-peptide, and anthropometrics were assessed by Pearson’s correlation while the Mann-Whitney U test was used to assess the differences in cord blood leptin, C-peptide, and insulin levels between groups. A significant difference (p < 0.001) was observed between the insulin levels of infants born LGA (18.73 ± 0.64 µlU/ml) and AGA (13.08 ± 0.43 µlU/ml). Consistently, A significant increase in concentration (p < 0.001) was observed in C-peptide levels of infants born LGA (9.32 ± 0.77 ng/ml) compared to AGA (5.44 ± 0.19 ng/ml). Cord blood leptin concentration of LGA infants (12.67 ng/mL ± 1.62) was significantly higher (p < 0.001) compared to the AGA infants (7.10 ng/mL ± 0.97). Significant positive correlations (p < 0.05) were observed among cord leptin levels and the birth weight, pre-pregnancy maternal weight and BMI between the infants of AGA and LGA. Consistently, a significant positive correlation (p < 0.05) was observed between the birth weight and the C peptide concentration. Significantly high concentrations of leptin, C-peptide and insulin levels in the cord blood of LGA infants suggest that they may be involved in regulating fetal growth. Although previous studies suggest comparatively high levels of body fat in the Asian population, values obtained in this study are not significantly different from values previously reported from Caucasian populations. According to this preliminary study, maternal pre-pregnancy BMI and weight may contribute as significant indicators of cord blood parameters of insulin resistance and possibly the birth weight of the newborn.

Keywords: large for gestational age, leptin, C-peptide, insulin

Procedia PDF Downloads 157

Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Atinderpal Kaur, Shweta Dang

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Our aim is to develop a nanoemulsion-based delivery system containing polyphenon 60 (P60) and ciprofloxacin (Cipro) for intravaginal delivery to treat urinary tract infection. In the present study Polyphenon 60 (P60) and ciprofloxacin (Cipro) were loaded in a single nano emulsion (NE) system via ultra-sonication technique and characterized for particle size, in vitro release and antibacterial efficacy against Bcl-2 level Escherichia coli bacteria. To determine in vivo pharmacokinetic parameters and intravaginal transportation of NE, gamma scintigraphy and biodistribution study was conducted by radiolabelling NE with technetium pertechnetate (99mTc). The preliminary antibacterial investigation showed synergy between these compounds with FICindex of 0.42. The developed formulation showed zeta potential +55.3 and particle size of 151.7 nm, with PDI of 0.196. The in vitro release percentage of P60 at the end of 7th hours was 94.8 ± 0.9 % whereas the release for Cipro was 75.1± 0.15 % in simulated vaginal media. MBC was identified and the findings demonstrated that in both ESBL (Extended Spectrum β- lactamase) and MBL (Metallo β- lactamase) cultures the P60+Cipro NE showed inhibition of growth of all the isolates at 2 mg/ml dilutions. The percentage per gram of radiolabelled drug was found (3.50±0.26) and (3.81±0.30) in kidney and urinary bladder, respectively at 3 h. From the findings, it was concluded that the developed P60+Cipro NE was transported efficiently throughout the target organs, had long duration of action and high biocompatibility via intravaginal administration as compared to oral administration.

Keywords: ciprofloxacin, gamma scintigraphy, intravaginal drug delivery, Polyphenon 60

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Authors: Satyananda Behera, Ritwik Sarkar

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In iron and steel industries, MgO–C refractories are widely used in basic oxygen furnaces, electric arc furnaces and steel ladles due to their excellent corrosion resistance, thermal shock resistance, and other excellent hot properties. Conventionally magnesia carbon refractories contain about 8-20 wt% of carbon but the use of carbon is also associate with disadvantages like oxidation, low fracture strength, high heat loss and higher carbon pick up in steel. So, MgO-C refractory having low carbon content without compromising the beneficial properties is the challenge. Nano carbon, having finer particles, can mix and distribute within the entire matrix uniformly and can result in improved mechanical, thermo-mechanical, corrosion and other refractory properties. Previous experiences with the use of nano carbon in low carbon MgO-C refractory have indicated an optimum range of use of nano carbon around 1 wt%. This optimum nano carbon content was used in MgO-C compositions with flaky graphite followed by aluminum and silicon metal powder as an anti-oxidant. These low carbon MgO-C refractory compositions were prepared by conventional manufacturing techniques. At the same time 16 wt. % flaky graphite containing conventional MgO-C refractory was also prepared parallel under similar conditions. The developed products were characterized for various refractory related properties. Nano carbon containing compositions showed better mechanical, thermo-mechanical properties, and oxidation resistance compared to that of conventional composition. Improvement in the properties is associated with the formation of in-situ ceramic phase-like aluminum carbide, silicon carbide, and magnesium aluminum spinel. Higher surface area and higher reactivity of N220 nano carbon black resulted in greater formation in-situ ceramic phases, even at a much lower amount. Nano carbon containing compositions were found to have improved properties in MgO-C refractories compared to that of the conventional ones at much lower total carbon content.

Keywords: N220nano carbon black, refractory properties, conventionally manufacturing techniques, conventional magnesia carbon refractories

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Authors: Clinton Adas

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Industrial animal farming contributes to numerous problems that humans face, and among these, antimicrobial resistance (AMR) has been identified by the World Health Organisation as a real possibility for the 21st Century. While numerous factors contribute to AMR, one of them is industrial animal farming and its effect on the food chain and environment. In 2017, livestock were given around 73% of all antibiotics worldwide to make them grow faster for profit purposes, to prevent illness caused by unhealthy living conditions, and to treat disease when it breaks out. Many of the antibiotics used provide little benefit to animals, and most are the same as those used by humans - including many deemed critical to human health that should be used sparingly. AMR contributes to millions of illnesses, and in 2019 was responsible for around 4.95 million deaths worldwide. It costs Europe around nine billion euros per year, while it costs the United States (US) around 20 billion dollars per year. While not a simple or quick solution, one way to begin to address the challenge of AMR and other harms from this type of farming is to focus on animal welfare as part of a One Health and Welfare approach, as better welfare requires less antibiotics usage, which may begin to break the cycle.

Keywords: animal and human welfare, industrial animal farming, antimicrobial resistance, one health and welfare, sustainable development goals

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Authors: B. S. Abdelwahed, B. B. Belkassem

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Beam-column joints are a critical part in reinforced concrete RC frames designed for inelastic response to several external loads. Investigating the behaviour of the exterior RC beam-column joints has attracted many researchers in the past decades due to its critical influence on the overall behaviour of RC moment-resisting frames subjected to lateral loads. One of the most critical zones in moment-resistant frames is the knee joints because of restraints associated with providing limited anchorage length to the beam and column longitudinal reinforcement in it and consequentially causes a lot of damage in such building frames. Previous numerical simulations focussed mainly on the exterior and interior joints, for knee joint further work is still needed to investigate its behaviour and discuss its affecting parameters. Structural response for an RC knee beam-column joint is performed in this study using LS-DYNA. Three-dimensional finite element (FE) models of an RC knee beam-column joint are described and verified with experimental results available in literature; this is followed by a parametric study to investigate the influence of the concrete compressive strength, the presence of lateral beams and increasing beam reinforcement ratio. It is shown that the concrete compressive strength has a significant effect on shear capacity, load-deflection characteristics and failure modes of an RC knee beam-column joints but to a certain limit, the presence of lateral beams increased the joint confinement and reduced the rate of concrete degradation in the joint after reaching ultimate joint capacity, added to that an increase in the maximum load resistance. Increasing beam reinforcement ratio is found to improve the flexural resistance of the anchored beam bars and increase the joint maximum load resistance.

Keywords: beam reinforcement ratio, joint confinement, numerical simulation, reinforced concrete beam-column joints, structural performance

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Authors: Tien S. H. Pham, Peter J. Mahon, Aimin Yu

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The detection of drug molecules by voltammetry has attracted great interest over the past years. However, many drug molecules exhibit poor electrochemical signals at common electrodes which result in low sensitivity in detection. An efficient way to overcome this problem is to modify electrodes with functional materials. Since discovered in 2004, graphene (or reduced graphene oxide) has emerged as one of the most studied two-dimensional carbon materials in condensed matter physics, electrochemistry, and so on due to its exceptional physicochemical properties. Additionally, the continuous development of technology has opened the new window for the successful fabrications of many novel graphene-based nanomaterials to serve in electrochemical analysis. This research aims to synthesize and characterize gold nanoparticle coated beta-cyclodextrin functionalized reduced graphene oxide (Au NP–β-CD–RGO) nanocomposites with highly conductive and strongly electro-catalytic properties as well as excellent supramolecular recognition abilities for the modification of electrodes. The electrochemical responses of ciprofloxacin at the as-prepared nanocomposite modified electrode was effectively amplified was much higher in comparison with that at the bare electrode. The linear concentration range was from 0.01 to 120 µM, with a detection limit of 2.7 nM using differential pulse voltammetry. Thus, Au NP–β-CD–RGO nanocomposite has great potential as an ideal material to construct sensitive sensors for the electrochemical determination of ciprofloxacin or similar antibacterial drugs in the future based on its excellent stability, selectivity, and reproducibility.

Keywords: Au nanoparticles, β-CD, ciprofloxacin, electrochemical determination, graphene based nanomaterials

Procedia PDF Downloads 188

Authors: Romaric Desbrousses, Lan Lin

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The objective of this study is to determine how Canadian seismic design provisions affect the column axial load resistance of moment-resisting frame reinforced concrete buildings subjected to the differential settlement of their foundation. To do so, two four-storey buildings are designed in accordance with the seismic design provisions of the Canadian Concrete Design Standards. One building is located in Toronto, which is situated in a moderate seismic hazard zone in Canada, and the other in Vancouver, which is in Canada’s highest seismic hazard zone. A finite element model of each building is developed using SAP 2000. A 100 mm settlement is assigned to the base of the building’s center column. The axial load resistance of the column is represented by the demand capacity ratio. The analysis results show that settlement-induced tensile axial forces have a particularly detrimental effect on the conventional settling columns of the Toronto buildings which fail at a much smaller settlement that those in the Vancouver buildings. The results also demonstrate that particular care should be taken in the design of columns in short-span buildings.

Keywords: Columns, Demand, Foundation differential settlement, Seismic design, Non-linear analysis

Procedia PDF Downloads 135

Authors: Riddhi Shukla, Rajeshri Patel, Prakruti Buch, Tejas Sharma, Mihir Raval, Navin Sheth

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Many classical drugs are claimed to have blood sugar lowering properties that make them valuable for people with or at high risk of type 2 diabetes. Vijaysar (Pterocarpus marsupium) and Gaumutra (Indian cow urine) both have been shown antidiabetic property since primordial time and both shows synergistic effect in combination for hypoglycaemic activity. The study was undertaken to investigate the hypoglycaemic and anti-diabetic effects of the combination of Vijaysar and Gaumutra which is a classical preparation mentioned in Ayurveda named as Pramehari ark. Rats with Type 2 diabetes which is induced by streptozotocin (STZ, 35mg/kg) given a high-fat diet for one month and compared with normal rats. Diabetic rats showed raised level of body weight, triglyceride (TG), total cholesterol, HDL, LDL, and D-glucose concentration and other serum, cardiac and hypertrophic parameters in comparison of normal rats. After treatment of different doses of drug the level of parameters like TG, total cholesterol, HDL, LDL, and D-glucose concentration found to be decreased in standard as well as in treatment groups. In addition treatment groups also found to be decreased in the level of serum markers, cardiac markers, and hypertrophic parameters. The findings demonstrated that Pramehari ark prevented the pathological progression of type 2 diabetes in rats.

Keywords: cow urine, hypoglycemic effect, synergic effect, type 2 diabetes, vijaysar

Procedia PDF Downloads 279

Authors: Gabriel S. De Oliveira, Patricia P. Adriani, Christophe Moriseau, Bruce D. Hammock, Felipe S. Chambergo

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Epoxide hydrolases (EHs) are enzymes that are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EHs have high biotechnological interest for the drug design and chemistry transformation for industries. In this study, we describe the identification of substrates and inhibitors of epoxide hydrolase enzyme from the filamentous fungus Trichoderma reesei (TrEH), and these inhibitors showed the fungal growth inhibitory activity. We have used the cloned enzyme and expressed in E. coli to develop the screening in the library of fluorescent substrates with the objective of finding the best substrate to be used in the identification of good inhibitors for the enzyme TrEH. The substrate (3-phenyloxiranyl)-acetic acid cyano-(6-methoxy-naphthalen-2-yl)-methyl ester showed the highest specific activity and was chosen for the next steps of the study. The inhibitors screening was performed in the library with more than three thousand molecules and we could identify the 6 best inhibitors. The IC50 of these molecules were determined in nM and all the best inhibitors have urea or amide in their structure, because It has been recognized that these groups fit well in the hydrolase catalytic pocket of the epoxide hydrolases. Then the growth of T. reesei in PDA medium containing these TrEH inhibitors was tested, and fungal growth inhibition activity was demonstrated with more than 60% of inhibition of fungus growth in the assay with the TrEH inhibitor with the lowest IC50. Understanding how this EH enzyme from T. reesei responds to inhibitors may contribute for the study of fungal metabolism and drug design against pathogenic fungi.

Keywords: epoxide hydrolases, fungal growth inhibition, inhibitor, Trichoderma reesei

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Authors: Mauro Masili, Liliane Ventura

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It is still controversial in the literature the ultraviolet (UV) radiation effects on the ocular media, but the World Health Organization has established safe limits on the exposure of eyes to UV radiation based on reports in literature. Sunglasses play an important role in providing safety, and their lenses should provide adequate UV filters. Regarding UV protection for ocular media, the resistance-to-irradiance test for sunglasses under many national standards requires irradiating lenses for 50 uninterrupted hours with a 450 W solar simulator. This artificial aging test may provide a corresponding evaluation of exposure to the sun. Calculating the direct and diffuse solar irradiance at a vertical surface and the corresponding radiant exposure for the entire year, we compare the latter with the 50-hour radiant exposure of a 450 W xenon arc lamp from a solar simulator required by national standards. Our calculations indicate that this stress test is ineffective in its present form. We provide evidence of the need to re-evaluate the parameters of the tests to establish appropriate safe limits against UV radiation. This work is potentially significant for scientists and legislators in the field of sunglasses standards to improve the requirements of sunglasses quality and safety.

Keywords: ISO 12312-1, solar simulator, sunglasses standards, UV protection

Procedia PDF Downloads 197