Search results for: plasma photonic crystal
611 Thermochromic Behavior of Fluoran-Based Mixtures Containing Liquid-Crystalline 4-n-Alkylbenzoic Acids as Color Developers
Authors: Magdalena Wilk-Kozubek, Jakub Pawłów, Maciej Czajkowski, Maria Zdończyk, Katarzyna Ślepokura, Joanna Cybińska
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Thermochromic materials belong to the family of intelligent materials that change their color in response to temperature changes; this ability is called thermochromism. Thermochromic behavior can be displayed by both isolated compounds and multicomponent mixtures. Fluoran leuco dye-based mixtures are well-known thermochromic systems used, for example, in heat-sensitive FAX paper. Weak acids often serve as color developers for such systems. As the temperature increases, the acids melt, and the mixtures become colored. The objective of this research is to determine the influence of acids showing a liquid crystalline nematic phase on the development of the fluoran dye. For this purpose, fluoran-based mixtures with 4-n-alkylbenzoic acids were prepared. The mixtures are colored at room temperature, but they become colorless upon the melting of the acids. The melting of acids is associated not only with a change in the color of the mixtures but also with a change in their emission color. Phase transitions were investigated by temperature-dependent powder X-ray diffraction and differential scanning calorimetry; nematic phases were visualized by polarized optical microscopy, and color and emission changes were studied by UV-Vis diffuse reflectance and photoluminescence spectroscopies, respectively. When 4-n-alkylbenzoic acids are used as color developers, the fluoran-based mixtures become colorless after the melting of the acids. This is because the melting of acids is accompanied by the transition from the crystalline phase to the nematic phase, in which the molecular arrangement of the acids does not allow the fluoran dye to be developed.Keywords: color developer, leuco dye, liquid crystal, thermochromism
Procedia PDF Downloads 91610 Mechanism of Melanin Inhibition of Morello Flavone- 7″- Sulphate and Sargaol extracts from Garcinia livingstonei (Clusiaceae): Homology Modelling, Molecular Docking, and Molecular Dynamics Simulations
Authors: Ncoza Dlova, Tivani Mashamba-Thompson
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Garcinia livingstonei (Clusiaceae) extracts, morelloflavone- 7″- sulphate and sargaol were shown to be effective against hyper-pigmentation through inhibition of tyrosinase enzyme, in vitro . The aim of this study is to elucidate the structural mechanism through which morelloflavone- 7″- sulphate and sargaol binds human tyrosinase. Implementing a homology model to construct a tyrosinase model using the crystal structure of a functional unit from Octopus hemocyanin (PDB: 1JS8) as a reference template enabled us to create a human tyrosinase model. Molecular dynamics and binding free energy calculations were optimized to enable molecular dynamics simulation of the copper dependent inhibitors. Results show the importance of the hydrogen bond formation morelloflavone- 7″- sulphate and sargaol between compound and active site residues. Both complexes demonstrated the metallic coordination between compound and arginine residue as well as copper ions within the active site. The comprehensive molecular insight gained from this study should be vital in understanding the binding mechanism morelloflavone- 7″- sulphate and sargaol. Moreover, these results will assist in the design of novel of metal ion dependent enzyme inhibitors as potential anti-hyper-pigmentation disorder therapies.Keywords: hyper-pigmentation disorders, dyschromia African skin, morelloflavone- 7″- sulphate, sagoal
Procedia PDF Downloads 399609 Wind Turbine Scaling for the Investigation of Vortex Shedding and Wake Interactions
Authors: Sarah Fitzpatrick, Hossein Zare-Behtash, Konstantinos Kontis
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Traditionally, the focus of horizontal axis wind turbine (HAWT) blade aerodynamic optimisation studies has been the outer working region of the blade. However, recent works seek to better understand, and thus improve upon, the performance of the inboard blade region to enhance power production, maximise load reduction and better control the wake behaviour. This paper presents the design considerations and characterisation of a wind turbine wind tunnel model devised to further the understanding and fundamental definition of horizontal axis wind turbine root vortex shedding and interactions. Additionally, the application of passive and active flow control mechanisms – vortex generators and plasma actuators – to allow for the manipulation and mitigation of unsteady aerodynamic behaviour at the blade inboard section is investigated. A static, modular blade wind turbine model has been developed for use in the University of Glasgow’s de Havilland closed return, low-speed wind tunnel. The model components - which comprise of a half span blade, hub, nacelle and tower - are scaled using the equivalent full span radius, R, for appropriate Mach and Strouhal numbers, and to achieve a Reynolds number in the range of 1.7x105 to 5.1x105 for operational speeds up to 55m/s. The half blade is constructed to be modular and fully dielectric, allowing for the integration of flow control mechanisms with a focus on plasma actuators. Investigations of root vortex shedding and the subsequent wake characteristics using qualitative – smoke visualisation, tufts and china clay flow – and quantitative methods – including particle image velocimetry (PIV), hot wire anemometry (HWA), and laser Doppler anemometry (LDA) – were conducted over a range of blade pitch angles 0 to 15 degrees, and Reynolds numbers. This allowed for the identification of shed vortical structures from the maximum chord position, the transitional region where the blade aerofoil blends into a cylindrical joint, and the blade nacelle connection. Analysis of the trailing vorticity interactions between the wake core and freestream shows the vortex meander and diffusion is notably affected by the Reynold’s number. It is hypothesized that the shed vorticity from the blade root region directly influences and exacerbates the nacelle wake expansion in the downstream direction. As the design of inboard blade region form is, by necessity, driven by function rather than aerodynamic optimisation, a study is undertaken for the application of flow control mechanisms to manipulate the observed vortex phenomenon. The designed model allows for the effective investigation of shed vorticity and wake interactions with a focus on the accurate geometry of a root region which is representative of small to medium power commercial HAWTs. The studies undertaken allow for an enhanced understanding of the interplay of shed vortices and their subsequent effect in the near and far wake. This highlights areas of interest within the inboard blade area for the potential use of passive and active flow control devices which contrive to produce a more desirable wake quality in this region.Keywords: vortex shedding, wake interactions, wind tunnel model, wind turbine
Procedia PDF Downloads 229608 Beliefs about the God of the Other in Intergroup Conflict: Experimental Results from Israel and Palestine
Authors: Crystal Shackleford, Michael Pasek, Allon Vishkin, Jeremy Ginges
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In the Middle East, conflict is often viewed as religiously motivated. In this context, an important question is how we think the religion of the other drives their behavior. If people see conflicts as religious, they may expect the belief of the other to motivate intergroup bias. Beliefs about the motivations of the other impact how we engage with them. Conflict may result if actors believe the other’s religion promotes parochialism. To examine how actors on the ground in Israel-Palestine think about the God of the other as it relates to the other’s behavior towards them, we ran two studies in winter 2019 with an online sample of Jewish Israelis and fieldwork with Palestinians in the West Bank. We asked participants to predict the behavior of an outgroup member participating in an economic game task, dividing the money between themselves and another person, who is either an ingroup or outgroup member. Our experimental manipulation asks participants to predict the behavior of the other when the other is thinking of their God. Both Israelis and Palestinians believed outgroup members would show in-group favoritism, and that group members would give more to their in-group when thinking of their God. We also found that participants thought outgroup members would give more to their own ingroup when thinking of God. In other words, Palestinians predicted that Israelis would give more to fellow Israelis when thinking of God, but also more to Palestinians. Our results suggest that religious belief is seen to promote universal moral reasoning, even in a context with over 70 years of intense conflict. More broadly, this challenges the narrative that religion necessarily motivates intractable conflict.Keywords: conflict, psychology, religion, meta-cognition, morality
Procedia PDF Downloads 134607 Effect of Metarhizium robertsii in Rhipicephalus microplus hemocytes
Authors: Jessica P. Fiorotti, Maria C. Freitas, Caio J. B. Coutinho-Rodrigues, Mariana G. Camargo, Emily S. Mesquita, Amanda R. C. Corval, Ricardo O. B. Bitencourt, Allan F. Marciano, Diva D. Spadacci-Morena, Patricia S. Golo, Isabele C. Angelo, Vania R. E. P. Bittencourt
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The bovine tick, Rhipicephalus microplus, is an arthropod of great importance in veterinary medicine leading to anemia, weight loss, animals' leather depreciation and also acting as a vector of many pathogens. In this way, the parasitism causes a loss of 3.24 billion dollars per year in Brazil. Knowingly, entomopathogenic fungi act as natural controller of some arthropods, acting mainly by active penetration through the cuticle. However, it can also act on the hemolymph and through the production of mycotoxins. Hemocytes are responsible for the cellular immune response and participate in the processes of phagocytosis, nodulation and encapsulation and may undergo changes when challenged by pathogens. The aim of the present study was to evaluate changes in R. microplus hemocytes after inoculation of Metarhizium robertsii using transmission electron microscopy. The isolate ARSEF 2575 and 200 engorged R. microplus females were used. The groups were divided into control, in which the females were inoculated with 5 μL of sterile distilled water solution and 0.1% Tween 80, and a group inoculated with 5 μL of fungal suspension at the concentration of 10⁷ conidia mL⁻¹. The experiment was performed in duplicate and each group contained 50 females. Twenty-four hours after fungal inoculation, hemolymph was collected through the cuticle dorsal surface perforation of the tick females. After collection, the hemolymph samples were centrifuged at 500 x g for 3 minutes at 4 °C, the plasma was discarded and the hemocyte pellet was resuspended in 50 μl PBS. The suspension material was fixed in 2% glutaraldehyde in Millonig buffer for three hours. After fixation, the material was centrifuged at 500 x g for 3 minutes, the supernatant was discarded and the cells were resuspended in a wash solution. Subsequently, the cells were post-fixed with 1% osmium tetroxide in phosphate buffer for one hour at room temperature and dehydrated in increasing concentrations of ethanol, and then embedded in Epon resin. The ultrathin sections were examined under the LEO EM 906E transmission electron microscopy at 80kV. The ultrastructural results revealed that.in control group, the cells were considered intact, in which the granulocytes were observed with granules of different electrodensities, intact mitochondria and cytoplasm without vacuolization. In addition, granulocytes showed plasma membrane projections similar to pseudopodia. Plasmatocytes presented as irregularly shaped cells, with the eccentric nucleus, agranular cytoplasm and some cells presented pseudopodia. Nevertheless, in the group exposed to the fungus, most of the cells presented in degeneration. The granulocytes found had fewer granules in the cytoplasm and more vacuoles. Plasmatocytes, after treatment, presented many vacuoles also in the cytoplasm and the lysosomes presented great amount of electrodense material in their interior. Thus, the results suggest that the fungus has a depressant action in the immune system of the tick, not only by the cell degranulation, but also suggesting that this leads to morphological changes in the hemocytes and may even trigger processes such as phagocytosis.Keywords: bovine tick, cellular defense, entomopathogenic fungi, immune response
Procedia PDF Downloads 185606 Adomian’s Decomposition Method to Generalized Magneto-Thermoelasticity
Authors: Hamdy M. Youssef, Eman A. Al-Lehaibi
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Due to many applications and problems in the fields of plasma physics, geophysics, and other many topics, the interaction between the strain field and the magnetic field has to be considered. Adomian introduced the decomposition method for solving linear and nonlinear functional equations. This method leads to accurate, computable, approximately convergent solutions of linear and nonlinear partial and ordinary differential equations even the equations with variable coefficients. This paper is dealing with a mathematical model of generalized thermoelasticity of a half-space conducting medium. A magnetic field with constant intensity acts normal to the bounding plane has been assumed. Adomian’s decomposition method has been used to solve the model when the bounding plane is taken to be traction free and thermally loaded by harmonic heating. The numerical results for the temperature increment, the stress, the strain, the displacement, the induced magnetic, and the electric fields have been represented in figures. The magnetic field, the relaxation time, and the angular thermal load have significant effects on all the studied fields.Keywords: Adomian’s decomposition method, magneto-thermoelasticity, finite conductivity, iteration method, thermal load
Procedia PDF Downloads 142605 Hot Deformation Behavior and Recrystallization of Inconel 718 Superalloy under Double Cone Compression
Authors: Wang Jianguo, Ding Xiao, Liu Dong, Wang Haiping, Yang Yanhui, Hu Yang
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The hot deformation behavior of Inconel 718 alloy was studied by uniaxial compression tests under the deformation temperature of 940~1040℃ and strain rate of 0.001-10s⁻¹. The double cone compression (DCC) tests develop strains range from 30% to the 79% strain including all intermediate values of stains at different temperature (960~1040℃). DCC tests were simulated by finite element software which shown the strain and strain rates distribution. The result shows that the peak stress level of the alloy decreased with increasing deformation temperature and decreasing strain rate, which could be characterized by a Zener-Hollomon parameter in the hyperbolic-sine equation. The characterization method of hot processing window containing recrystallization volume fraction and average grain size was proposed for double cone compression test of uniform coarse grain, mixed crystal and uniform fine grain double conical specimen in hydraulic press and screw press. The results show that uniform microstructures can be obtained by low temperature with high deformation followed by high temperature with small deformation on the hydraulic press and low temperature, medium deformation, multi-pass on the screw press. The two methods were applied in industrial forgings process, and the forgings with uniform microstructure were obtained successfully.Keywords: inconel 718 superalloy, hot processing windows, double cone compression, uniform microstructure
Procedia PDF Downloads 214604 Assessment of Naturally Occurring Radionuclides of the Surface Water in Vaal River, South Africa
Authors: Kgantsi B. T., Ochwelwang A. R., Mathuthu M., Jegede O. A.
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Anthropogenic activities near water bodies contribute to poor water quality, which degrades the condition of the biota and elevates the risk to human health. The Vaal River is essential in supplying Gauteng and neighboring regions of South Africa with portable water for a variety of consumers and industries. Consequently, it is necessary to monitor and assess the radioactive risk in relation to the river's water quality. This study used an inductive coupled plasma mass spectrometer (ICPMS) to analyze the radionuclide activity concentration in the Vaal River, South Africa. Along with thorium and potassium, the total uranium concentration was calculated using the isotopic content of uranium. The elemental concentration of ²³⁸U, ²³⁵U, ²³⁴U, ²³²Th, and 40K were translated into activity concentrations. To assess the water safety for all users and consumers, all values were compared to world average activity concentrations 35, 30, and 400 Bqkg⁻¹ for ²³⁸U, ²³⁴Th, and ⁴⁰K, respectively, according to the UNSCEAR report. The results will serve as a database for further monitoring and evaluation of the radionuclide from the river, taking cognisance of potential health hazards.Keywords: Val Rivers, ICPMS, uranium, risks
Procedia PDF Downloads 158603 Rapid, Label-Free, Direct Detection and Quantification of Escherichia coli Bacteria Using Nonlinear Acoustic Aptasensor
Authors: Shilpa Khobragade, Carlos Da Silva Granja, Niklas Sandström, Igor Efimov, Victor P. Ostanin, Wouter van der Wijngaart, David Klenerman, Sourav K. Ghosh
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Rapid, label-free and direct detection of pathogenic bacteria is critical for the prevention of disease outbreaks. This paper for the first time attempts to probe the nonlinear acoustic response of quartz crystal resonator (QCR) functionalized with specific DNA aptamers for direct detection and quantification of viable E. coli KCTC 2571 bacteria. DNA aptamers were immobilized through biotin and streptavidin conjugation, onto the gold surface of QCR to capture the target bacteria and the detection was accomplished by shift in amplitude of the peak 3f signal (3 times the drive frequency) upon binding, when driven near fundamental resonance frequency. The developed nonlinear acoustic aptasensor system demonstrated better reliability than conventional resonance frequency shift and energy dissipation monitoring that were recorded simultaneously. This sensing system could directly detect 10⁽⁵⁾ cells/mL target bacteria within 30 min or less and had high specificity towards E. coli KCTC 2571 bacteria as compared to the same concentration of S.typhi bacteria. Aptasensor response was observed for the bacterial suspensions ranging from 10⁽⁵⁾-10⁽⁸⁾ cells/mL. Conclusively, this nonlinear acoustic aptasensor is simple to use, gives real-time output, cost-effective and has the potential for rapid, specific, label-free direction detection of bacteria.Keywords: acoustic, aptasensor, detection, nonlinear
Procedia PDF Downloads 556602 Solid-State Synthesis Approach and Optical study of Red Emitting Phosphors Li₃BaSrxCa₁₋ₓEu₂.₇Gd₀.₃(MoO₄)₈ for White LEDs
Authors: Priyansha Sharma, Sibani Mund, Sivakumar Vaidyanathan
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Solid-state synthesis methods were used for the synthesis of pure red emissive Li¬3BaSrxCa(1-x)Eu2.7Gd0.3(MoO4)8 (x = 0.0 to 1.0) phosphors, XRD, SEM, and FTIR spectra were used to characterize the materials, and their optical properties were thoroughly investigated. PL studies were examined at different excitations 230 nm, 275nm, 465nm, and 395 nm. All the spectra show similar emissions with the highest transition at 616 nm due to ED transition. The given phosphor Li¬3BaSr0.25Ca0.75Eu2.7Gd0.3(MoO4)8 shows the highest intensity and is thus chosen for the temperature-dependent and Quantum yield study. According to the PL investigation, the phosphor-containing Eu3+ emits red light due to the (5D0 7F2) transition. The excitation analysis shows that all of the Eu3+ activated phosphors exhibited broad absorption due to the charge transfer band, O2-Mo6+, O2-Eu3+ transition, as well as narrow absorption bands related to the Eu3+ ion's 4f-4f electronic transition. Excitation spectra show Charge transfer band at 275 nm shows the highest intensity. The primary band in the spectra refers to Eu3+ ions occupying the lattice's non-centrosymmetric location. All of the compositions are monoclinic crystal structures with space group C2/c and match with reference powder patterns. The thermal stability of the 3BaSr0.25Ca0.75Eu2.7Gd0.3(MoO4)8 phosphor was investigated at (300 k- 500 K) as well as at low temperature from (20 K to 275 K) to be utilized for red and white LED fabrication. The Decay Lifetime of all the phosphor was measured. The best phosphor was used for White and Red LED fabrication.Keywords: PL, phosphor, quantum yield, white LED
Procedia PDF Downloads 65601 Theoretical and Experimental Investigation of Binder-free Trimetallic Phosphate Nanosheets
Authors: Iftikhar Hussain, Muhammad Ahmad, Xi Chen, Li Yuxiang
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Transition metal phosphides and phosphates are newly emerged electrode material candidates in energy storage devices. For the first time, we report uniformly distributed, interconnected, and well-aligned two-dimensional nanosheets made from trimetallic Zn-Co-Ga phosphate (ZCGP) electrode materials with preserved crystal phase. It is found that the ZCGP electrode material exhibits about 2.85 and 1.66 times higher specific capacity than mono- and bimetallic phosphate electrode materials at the same current density. The trimetallic ZCGP electrode exhibits superior conductivity, lower internal resistance (IR) drop, and high Coulombic efficiency compared to mono- and bimetallic phosphate. The charge storage mechanism is studied for mono- bi- and trimetallic electrode materials, which illustrate the diffusion-dominated battery-type behavior. By means of density functional theory (DFT) calculations, ZCGP shows superior metallic conductivity due to the modified exchange splitting originating from 3d-orbitals of Co atoms in the presence of Zn and Ga. Moreover, a hybrid supercapacitor (ZCGP//rGO) device is engineered, which delivered a high energy density (ED) of 40 W h kg⁻¹ and a high-power density (PD) of 7,745 W kg⁻¹, lighting 5 different colors of light emitting diodes (LEDs). These outstanding results confirm the promising battery-type electrode materials for energy storage applications.Keywords: trimetallic phosphate, nanosheets, DFT calculations, hybrid supercapacitor, binder-free, synergistic effect
Procedia PDF Downloads 203600 Sensitive Determination of Copper(II) by Square Wave Anodic Stripping Voltammetry with Tetracarbonylmolybdenum(0) Multiwalled Carbon Nanotube Paste Electrode
Authors: Illyas Md Isa, Mohamad Idris Saidin, Mustaffa Ahmad, Norhayati Hashim
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A highly selective and sensitive carbon paste electrode modified with multiwall carbon nanotubes and 2,6–diacetylpyridine-di-(1R)–(-)–fenchone diazine tetracarbonylmolybdenum(0) complex was used for determination of trace amounts of Cu(II) using square wave anodic stripping voltammetry (SWASV). The influences of experimental variables on the proposed electrode such as pH, supporting electrolyte, preconcentration potential and time, and square wave parameters were investigated. Under optimal conditions, the proposed electrode showed a linear relationship with concentration in the range of 1.0 × 10–10 to 1.0 × 10– 6 M Cu(II) with a limit of detection 8.0 × 10–11 M. The relative standard deviation (n = 5) for a solution containing 1.0 × 10– 6 M of Cu(II) was 0.036. The presence of various cations (in 10 and 100-folds concentration) did not interfere. Electrochemical impedance spectroscopy (EIS) showed that the charge transfer at the electrode-solution interface was favourable. The proposed electrode was applied for the determination of Cu(II) in several water samples. Results agreed very well with those obtained by inductively coupled plasma-optical emission spectrometry. The modified electrode was then proposed as an alternative for determination of Cu(II).Keywords: chemically modified electrode, Cu(II), square wave anodic stripping voltammetry, tetracarbonylmolybdenum(0)
Procedia PDF Downloads 265599 Synthesis, Characterization, Theoretical Crystal Structures and Antitubercular Activity Study of (E)-N'-(2,4-Dihydroxybenzylidene) Nicotinohydrazide and Some of Its Metal Complexes
Authors: Ogunniran Kehinde Olurotimi, Adekoya Joseph, Ehi-Eromosele Cyril, Mehdi Shihab, Mesubi Adediran, Tadigoppula Narender
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Nicotinic acid hydrazide and 2,4-dihydoxylbenzaldehyde were condensed at 20°C to form an acylhydrazone (H3L) with ONO coordination pattern. The structure of the acylhydrazone was elucidated by using CHN analyzer, ESI mass spectrometry, IR, 1H NMR, 13C NMR and 2D NMR such as COSY and HSQC. Thereafter, five novel metal complexes [Mn(II), Fe(II), Pt(II) Zn(II) and Pd(II)] of the hydrazone ligand were synthesized and their structural characterization were achieved by several physicochemical methods, namely elemental analysis, electronic spectra, infrared, EPR, molar conductivity and powder X-ray diffraction studies. Structural geometries of some of the compounds were supported by using Hyper Chem-8 program for the molecular mechanics and semi-empirical calculations. The stability energy (E) and electron potentials (eV) for the frontier molecules were calculated by using PM3 method. An octahedral geometry was suggested for both Pd(II) and Zn(II) complexes while both Mn(II) and Fe(II) complexes conformed with tetrahedral pyramidal. However, Pt(II) complex agreed with tetrahedral geometry. In vitro antitubercular activity study of the ligand and the metal complexes were evaluated against Mycobacterium tuberculosis, H37Rv, by using micro-diluted method. The results obtained revealed that (PtL1) (MIC = 0.56 µg/mL), (ZnL1) (MIC = 0.61 µg/mL), (MnL1) (MIC = 0.71 µg/mL) and (FeL1) (MIC = 0.82 µg/mL), exhibited a significant activity when compared with first line drugs such as isoniazid (INH) (MIC = 0.9 µg/mL). H3L1 exhibited lesser antitubercular activity with MIC value of 1.02 µg/mL. However, the metal complexes displayed higher cytoxicity but were found to be non-significant different (P ˂ 0.05) to isoniazid drug.Keywords: hydrazones, electron spin resonance, thermogravimetric, powder X-ray diffraction, antitubercular agents
Procedia PDF Downloads 262598 Establishment of Farmed Fish Welfare Biomarkers Using an Omics Approach
Authors: Pedro M. Rodrigues, Claudia Raposo, Denise Schrama, Marco Cerqueira
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Farmed fish welfare is a very recent concept, widely discussed among the scientific community. Consumers’ interest regarding farmed animal welfare standards has significantly increased in the last years posing a huge challenge to producers in order to maintain an equilibrium between good welfare principles and productivity, while simultaneously achieve public acceptance. The major bottleneck of standard aquaculture is to impair considerably fish welfare throughout the production cycle and with this, the quality of fish protein. Welfare assessment in farmed fish is undertaken through the evaluation of fish stress responses. Primary and secondary stress responses include release of cortisol and glucose and lactate to the blood stream, respectively, which are currently the most commonly used indicators of stress exposure. However, the reliability of these indicators is highly dubious, due to a high variability of fish responses to an acute stress and the adaptation of the animal to a repetitive chronic stress. Our objective is to use comparative proteomics to identify and validate a fingerprint of proteins that can present an more reliable alternative to the already established welfare indicators. In this way, the culture conditions will improve and there will be a higher perception of mechanisms and metabolic pathway involved in the produced organism’s welfare. Due to its high economical importance in Portuguese aquaculture Gilthead seabream will be the elected species for this study. Protein extracts from Gilthead Seabream fish muscle, liver and plasma, reared for a 3 month period under optimized culture conditions (control) and induced stress conditions (Handling, high densities, and Hipoxia) are collected and used to identify a putative fish welfare protein markers fingerprint using a proteomics approach. Three tanks per condition and 3 biological replicates per tank are used for each analisys. Briefly, proteins from target tissue/fluid are extracted using standard established protocols. Protein extracts are then separated using 2D-DIGE (Difference gel electrophoresis). Proteins differentially expressed between control and induced stress conditions will be identified by mass spectrometry (LC-Ms/Ms) using NCBInr (taxonomic level - Actinopterygii) databank and Mascot search engine. The statistical analysis is performed using the R software environment, having used a one-tailed Mann-Whitney U-test (p < 0.05) to assess which proteins were differentially expressed in a statistically significant way. Validation of these proteins will be done by comparison of the RT-qPCR (Quantitative reverse transcription polymerase chain reaction) expressed genes pattern with the proteomic profile. Cortisol, glucose, and lactate are also measured in order to confirm or refute the reliability of these indicators. The identified liver proteins under handling and high densities induced stress conditions are responsible and involved in several metabolic pathways like primary metabolism (i.e. glycolysis, gluconeogenesis), ammonia metabolism, cytoskeleton proteins, signalizing proteins, lipid transport. Validition of these proteins as well as identical analysis in muscle and plasma are underway. Proteomics is a promising high-throughput technique that can be successfully applied to identify putative welfare protein biomarkers in farmed fish.Keywords: aquaculture, fish welfare, proteomics, welfare biomarkers
Procedia PDF Downloads 148597 Cocrystal of Mesalamine for Enhancement of Its Biopharmaceutical Properties, Utilizing Supramolecular Chemistry Approach
Authors: Akshita Jindal, Renu Chadha, Maninder Karan
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Supramolecular chemistry has gained recent eminence in a flurry of research documents demonstrating the formation of new crystalline forms with potentially advantageous characteristics. Mesalamine (5-amino salicylic acid) belongs to anti-inflammatory class of drugs, is used to treat ulcerative colitis and Crohn’s disease. Unfortunately, mesalamine suffer from poor solubility and therefore very low bioavailability. This work is focused on preparation and characterization of cocrystal of mesalamine with nicotinamide (MNIC) a coformer of GRAS status. Cocrystallisation was achieved by solvent drop grinding in stoichiometric ratio of 1:1 using acetonitrile as solvent and was characterized by various techniques including DSC (Differential Scanning Calorimetry), PXRD (X-ray Powder Diffraction), and FTIR (Fourier Transform Infrared Spectrometer). The co-crystal depicted single endothermic transitions (254°C) which were different from the melting peaks of both drug (288°C) and coformer (128°C) indicating the formation of a new solid phase. Different XRPD patterns and FTIR spectrums for the co-crystals from those of individual components confirms the formation of new phase. Enhancement in apparent solubility study and intrinsic dissolution study showed effectiveness of this cocrystal. Further improvement in pharmacokinetic profile has also been observed with 2 folds increase in bioavailability. To conclude, our results show that application of nicotinamide as a coformer is a viable approach towards the preparation of cocrystals of potential drug molecule having limited solubility.Keywords: cocrystal, mesalamine, nicotinamide, solvent drop grinding
Procedia PDF Downloads 164596 Intertextuality in Choreography: Investigation of Text and Movements in Making Choreography
Authors: Muhammad Fairul Azreen Mohd Zahid
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Speech, text, and movement intensify aspects of creating choreography by connecting with emotional entanglements, tradition, literature, and other texts. This research focuses on the practice as research that will prioritise the choreography process as an inquiry approach. With the driven context, the study intervenes in critical conjunctions of choreographic theory, bringing together new reflections on the moving body, spaces of action, as well as intertextuality between text and movements in making choreography. Throughout the process, the researcher will introduce the level of deliberation from speech through movements and text to express emotion within a narrative context of an “illocutionary act.” This practice as research will produce a different meaning from the “utterance text” to “utterance movements” in the perspective of speech acts theory by J.L Austin based on fragmented text from “pidato adat” which has been used as opening speech in Randai. Looking at the theory of deconstruction by Jacque Derrida also will give a different meaning from the text. Nevertheless, the process of creating the choreography will also help to lay the basic normative structure implicit in “constative” (statement text/movement) and “performative” (command text/movement). Through this process, the researcher will also look at several methods of using text from two works by Joseph Gonzales, “Becoming King-The Pakyung Revisited” and Crystal Pite's “The Statement,” as references to produce different methods in making choreography. The perspective from the semiotic foundation will support how occurrences within dance discourses as texts through a semiotic lens. The method used in this research is qualitative, which includes an interview and simulation of the concept to get an outcome.Keywords: intertextuality, choreography, speech act, performative, deconstruction
Procedia PDF Downloads 93595 Design and Implementation Wireless System by Using Microcontrollers.Application for Drive Acquisition System with Multiple Sensors
Authors: H. Fekhar
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Design and implementation acquisition system using radio frequency (RF) ASK module and micro controllers PIC is proposed in this work. The paper includes hardware and software design. The design tools are divided into two units , namely the sender MCU and receiver.The system was designed to measure temperatures of two furnaces and pressure pneumatic process. The wireless transmitter unit use the 433.95 MHz band directly interfaced to micro controller PIC18F4620. The sender unit consists of temperatures-pressure sensors , conditioning circuits , keypad GLCD display and RF module.Signal conditioner converts the output of the sensors into an electric quantity suitable for operation of the display and recording system.The measurements circuits are connected directly to 10 bits multiplexed A/D converter.The graphic liquid crystal display (GLCD) is used . The receiver (RF) module connected to a second microcontroller ,receive the signal via RF receiver , decode the Address/data and reproduces the original data . The strategy adopted for establishing communication between the sender MCU and receiver uses the specific protocol “Header, Address and data”.The communication protocol dealing with transmission and reception have been successfully implemented . Some experimental results are provided to demonstrate the effectiveness of the proposed wireless system. This embedded system track temperatures – pressure signal reasonably well with a small error.Keywords: microcontrollers, sensors, graphic liquid cristal display, protocol, temperature, pressure
Procedia PDF Downloads 455594 Risk Prediction Based on Heavy Metal Distribution in Groundwater
Authors: Rama Bhattacharyya, S. N. Ojha, Umesh K. Singh
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Anthropogenic control on groundwater chemistry has emerged as a critical concern now-a-days, especially in the industrial areas. In view of this, a comprehensive study on the distribution of the heavy metal in the groundwater was conducted to investigate the impact of urbanization in the aquatic media. Water samples either from well or borehole from Fourty different sites in and around, Durgapur, West Bengal were collected for this purpose. The samples were analyzed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for Calcium (Ca), Cobalt (Co), Chromium (Cr), Copper (Cu), Iron (Fe), Potassium (K), Magnesium (Mg), Manganese (Mn), Sodium (Na), Nickel (Ni), Lead (Pb), Zinc (Zn) content and the levels were compared with WHO specified maximum contaminant level as well as permissible limits given by the Bureau of Indian Standards (BIS). The result obtained from the present study indicates a significant risk to the population of this important emerging ‘smart city’ of eastern India. Because of the toxicity of these metals and the fact that for many tube-wells, dug-wells and bore-wells are the only sources of the water supply for a major fraction of the population in this environment. In this study, an attempt has been made to develop metal contamination risk map.Keywords: heavy metals, ground water, maximum contamination level, ICP-MS
Procedia PDF Downloads 208593 Development of a Biomaterial from Naturally Occurring Chloroapatite Mineral for Biomedical Applications
Authors: H. K. G. K. D. K. Hapuhinna, R. D. Gunaratne, H. M. J. C. Pitawala
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Hydroxyapatite is a bioceramic which can be used for applications in orthopedics and dentistry due to its structural similarity with the mineral phase of mammalian bones and teeth. In this study, it was synthesized, chemically changing natural Eppawala chloroapatite mineral as a value-added product. Sol-gel approach and solid state sintering were used to synthesize products using diluted nitric acid, ethanol and calcium hydroxide under different conditions. Synthesized Eppawala hydroxyapatite powder was characterized using X-ray Fluorescence (XRF), X-ray Powder Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) in order to find out its composition, crystallinity, presence of functional groups, bonding type, surface morphology, microstructural features, and thermal dependence and stability, respectively. The XRD results reflected the formation of a hexagonal crystal structure of hydroxyapatite. Elementary composition and microstructural features of products were discussed based on the XRF and SEM results of the synthesized hydroxyapatite powder. TGA and DSC results of synthesized products showed high thermal stability and good material stability in nature. Also, FTIR spectroscopy results confirmed the formation of hydroxyapatite from apatite via the presence of hydroxyl groups. Those results coincided with the FTIR results of mammalian bones including human bones. The study concludes that there is a possibility of producing hydroxyapatite using commercially available Eppawala chloroapatite in Sri Lanka.Keywords: dentistry, Eppawala chlorapatite, hydroxyapatite, orthopedics
Procedia PDF Downloads 232592 Effects of Oral Resveratrol Supplementation on Inflammation and Quality of Life in Patients with Ulcerative Colitis
Authors: M. Samsami, A. Hekmatdoost, N. Ebrahimi Daryani, P. Rezanejad Asl
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Ulcerative colitis (UC) is an inflammatory bowel disease in which immune and inflammatory factors are thought to be effective in this disease. Resveratrol is an antioxidant and anti-inflammatory compound. This study determined the effects of resveratrol compound on inflammatory factors in patients with ulcerative colitis. This study was a double-blind randomized clinical trial conducted on 50 patients with UC. Subjects received one capsule daily for 6 wk of either resveratrol (500 mg) or a placebo. Inflammatory factors, anthropometric measures, and IBDQ-9 (Inflammatory Bowel Disease Questionnaire-9) scores were assessed at baseline and at the end of the study. STATA12 software was used for data analysis. No significant differences were found in the background variables between the two groups at baseline. The results indicated that resveratrol supplementation for 6 week significantly decreased plasma levels of TNF-a and hs-CRP and the activity of NF-κB over the placebo group (p<0.001). Significant differences remained after adjustment for vitamin C (p<0.0001). The IBDQ-9 scores increased significantly in the resveratrol group over the placebo group (p<0.001). The findings of this study showed that resveratrol supplementation can be useful in patients with ulcerative colitis.Keywords: IBD, inflammation, resveratrol, ulcerative colitis
Procedia PDF Downloads 399591 Determination of Sintering Parameters of TiB₂ – Ti₃SiC₂ Composites
Authors: Bilge Yaman Islak, Erhan Ayas
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The densification behavior of TiB₂ – Ti₃SiC₂ composites is investigated for temperatures in the range of 1200°C to 1400°C, for the pressure of 40 and 50MPa, and for holding time between 15-30 min by spark plasma sintering (SPS) technique. Ti, Si, TiC and 5 wt.% TiB₂ were used to synthesize TiB₂ – Ti₃SiC₂ composites and the effect of different sintering parameters on the densification and phase evolution of these composites were investigated. The bulk densities were determined by using the Archimedes method. The polished and fractured surfaces of the samples were examined using a scanning electron microscope equipped with an energy dispersive spectroscopy (EDS). The phase analyses were accomplished by using the X-Ray diffractometer. Sintering temperature and holding time are found to play a dominant role in the phase development of composites. TiₓCᵧ and TiSi₂ secondary phases were found in 5 wt.%TiB₂ – Ti₃SiC₂ composites densified at 1200°C and 1400°C under the pressure of 40 MPa, due to decomposition of Ti₃SiC₂. The results indicated that 5 wt.%TiB₂ – Ti₃SiC₂ composites were densified into the dense parts with a relative density of 98.77% by sintering at 1300 °C, for 15 min, under a pressure of 50 MPa via SPS without the formation of any other ancillary phase. This work was funded and supported by Scientific Research Projects Commission of Eskisehir Osmangazi University with the Project Number 201915C103 (2019-2517).Keywords: densification, phase evolution, sintering, TiB₂ – Ti₃SiC₂ composites
Procedia PDF Downloads 137590 Process Monitoring Based on Parameterless Self-Organizing Map
Authors: Young Jae Choung, Seoung Bum Kim
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Statistical Process Control (SPC) is a popular technique for process monitoring. A widely used tool in SPC is a control chart, which is used to detect the abnormal status of a process and maintain the controlled status of the process. Traditional control charts, such as Hotelling’s T2 control chart, are effective techniques to detect abnormal observations and monitor processes. However, many complicated manufacturing systems exhibit nonlinearity because of the different demands of the market. In this case, the unregulated use of a traditional linear modeling approach may not be effective. In reality, many industrial processes contain the nonlinear and time-varying properties because of the fluctuation of process raw materials, slowing shift of the set points, aging of the main process components, seasoning effects, and catalyst deactivation. The use of traditional SPC techniques with time-varying data will degrade the performance of the monitoring scheme. To address these issues, in the present study, we propose a parameterless self-organizing map (PLSOM)-based control chart. The PLSOM-based control chart not only can manage a situation where the distribution or parameter of the target observations changes, but also address the nonlinearity of modern manufacturing systems. The control limits of the proposed PLSOM chart are established by estimating the empirical level of significance on the percentile using a bootstrap method. Experimental results with simulated data and actual process data from a thin-film transistor-liquid crystal display process demonstrated the effectiveness and usefulness of the proposed chart.Keywords: control chart, parameter-less self-organizing map, self-organizing map, time-varying property
Procedia PDF Downloads 264589 Effect of Different Parameters on the Swelling Behaviour of Thermo-Responsive Elastomers in a Nematogenic Solvent
Authors: Nouria Bouchikhi, Soufiane Bedjaoui, C. Tewfik Bouchaour, Lamia Alachaher Bedjaoui, Ulrich Maschke
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Swelling properties and phase diagrams of binary systems composed of liquid crystalline networks and a low molecular mass liquid crystal (LMWLC) have been investigated. The networks were prepared by ultraviolet (UV) irradiation of reactive mixtures including a monomer, a cross-linking agent and a photo-initiator. These networks were prepared using two cross-linking agents: 1,6 hexanedioldiacrylate (HDDA) and a mesogenic acrylic acid 6-(4’-(6-acryloyloxy-hexyloxy) biphenyl-4-yl oxy) hexyl ester (AHBH). The obtained dry networks were characterized by differential scanning calorimetry, and immersed in an excess of a LMWLC solvent 4-cyano-4’-pentylbiphenyl (5CB), forming polymer gels. A detailed study by polarized optical microscopy allowed to determine the swelling degree of the gels and to follow the phase behavior of the solvent inside the polymer matrix in a wide range of temperature. It has been found that the gels undergo a sharp decrease of their swelling degree in response to an infinitesimal change of temperature. This finding adds new and interesting aspects on the actuators applications. We have subsequently explored the effect of different parameters on volume phase transition of these liquid crystalline materials. Such as the cross-linking density (CD), a nature of cross-linking agent and the photo initiator concentration.Keywords: cross-linking density, liquid crystalline elastomers, phase diagrams, swelling
Procedia PDF Downloads 325588 New Highly-Scalable Carbon Nanotube-Reinforced Glasses and Ceramics
Authors: Konstantinos G. Dassios, Guillaume Bonnefont, Gilbert Fantozzi, Theodore E. Matikas, Costas Galiotis
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We report herein the development and preliminary mechanical characterization of fully-dense multi-wall carbon nanotube (MWCNT)-reinforced ceramics and glasses based on a completely new methodology termed High Shear Compaction (HSC). The tubes are introduced and bound to the matrix grains by aid of polymeric binders to form flexible green bodies which are sintered and densified by spark plasma sintering to unprecedentedly high densities of 100% of the pure-matrix value. The strategy was validated across a PyrexTM glass / MWCNT composite while no identifiable factors limit application to other types of matrices. Non-destructive evaluation, based on ultrasonics, of the dynamic mechanical properties of the materials including elastic, shear and bulk modulus as well as Poisson’s ratio showed optimum property improvement at 0.5 %wt tube loading while evidence of nanoscale-specific energy dissipative characteristics acting complementary to nanotube bridging and pull-out indicate a high potential in a wide range of reinforcing and multifunctional applications.Keywords: ceramic matrix composites, carbon nanotubes, toughening, ultrasonics
Procedia PDF Downloads 368587 Synthesis, Structural, Spectroscopic and Nonlinear Optical Properties of New Picolinate Complex of Manganese (II) Ion
Authors: Ömer Tamer, Davut Avcı, Yusuf Atalay
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Novel picolinate complex of manganese(II) ion, [Mn(pic)2] [pic: picolinate or 2-pyridinecarboxylate], was prepared and fully characterized by single crystal X-ray structure determination. The manganese(II) complex was characterized by FT-IR, FT-Raman and UV–Vis spectroscopic techniques. The C=O, C=N and C=C stretching vibrations were found to be strong and simultaneously active in IR and spectra. In order to support these experimental techniques, density functional theory (DFT) calculations were performed at Gaussian 09W. Although the supramolecular interactions have some influences on the molecular geometry in solid state phase, the calculated data show that the predicted geometries can reproduce the structural parameters. The molecular modeling and calculations of IR, Raman and UV-vis spectra were performed by using DFT levels. Nonlinear optical (NLO) properties of synthesized complex were evaluated by the determining of dipole moment (µ), polarizability (α) and hyperpolarizability (β). Obtained results demonstrated that the manganese(II) complex is a good candidate for NLO material. Stability of the molecule arising from hyperconjugative interactions and charge delocalization was analyzed using natural bond orbital (NBO) analysis. The highest occupied and the lowest unoccupied molecular orbitals (HOMO and LUMO) which is also known the frontier molecular orbitals were simulated, and obtained energy gap confirmed that charge transfer occurs within manganese(II) complex. Molecular electrostatic potential (MEP) for synthesized manganese(II) complex displays the electrophilic and nucleophilic regions. From MEP, the the most negative region is located over carboxyl O atoms while positive region is located over H atoms.Keywords: DFT, picolinate, IR, Raman, nonlinear optic
Procedia PDF Downloads 494586 The Overexpression of Horsegram MURLK Improves Regulation of Cell Death and Defense Responses to Microbial Pathogens
Authors: Shikha Masand, Sudesh Kumar Yadav
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Certain protein kinases have been shown to be crucial for plant cell signaling pathways associated with plant immune responses. Here we identified a horsegram [Macrotyloma uniflorum (Lam.) Verdc.] malectin-like leucine rich receptor-like protein kinase (RLK) gene MuRLK. The functional MuRLK protein preferentially binds to mannose and N-acetyl glucosamine residues. MuRLK exists in the cytoplasm and also localizes to the plasma membrane of plant cells via its N-terminus. Over-expression of MuRLK in Arabidopsis enhances the basal resistance to infection with Pseudomonas syringae pv. tomato, Alternaria brassicicola and Hyaloperonospora arabidopsidis, are associated with elevated ROS bursts, MAPK activation, thus ultimately leading to hypersensitive cell death. Moreover, salicylic acid-dependent and jasmonic acid-dependent defense responses are also enhanced in the MuRLK-overexpressed plants that lead to HR-induced cell death. Together, these results suggest that MuRLK plays a key role in the regulation of plant cell death, early and late defense responses after the recognition of microbial pathogens.Keywords: horsegram, Pseudomonas syringae pv. tomato, MuRLK, ROS burst, cell death, plant defense
Procedia PDF Downloads 244585 In vivo Therapeutic Potential of Biologically Synthesized Silver Nanoparticles
Authors: Kalakotla Shanker, G. Krishna Mohan
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Nowadays, nanoparticles are being used in pharmacological studies for their exclusive properties such as small size, more surface area, biocompatibility and enhanced solubility. In view of this, the present study aimed to evaluate the antihyperglycemic potential of biologically synthesized silver nanoparticles (BSSNPs) and Gymnema sylvestre (GS) extract. The SEM and SEM analysis divulges that the BSSNPs were spherical in shape. EDAX spectrum exhibits peaks for the presence of silver, carbon, and oxygen atoms in the range of 1.0-3.1 keV. FT-IR reveals the binding properties of active bio-constituents responsible for capping and stabilizing BSSNPs. The results showed increased blood glucose, huge loss in body weight and downturn in plasma insulin. The GS extract (200 mg/kg, 400 mg/kg), BSSNPs (100 mg/kg, 200 mg/kg) and metformin 50 mg/kg were administered to the diabetic rats. BSSNPs at a dose level of 200 mg/kg (b.wt.p.o.) showed significant inhibition of (p<0.001) blood glucose levels as compared with GS extract treated group. The results obtained from study indicate that the BSSNP shows potent anti-diabetic activity.Keywords: biological silver nanoparticles, G. sylvetre, gymnemic acid, streptozotocin, Wistar rats, antihyperglycemic activity, anti-hyperlipidemic activity
Procedia PDF Downloads 300584 Association of Lipoprotein Lipase Gene (HindIII rs320) Polymorphisms with Moderate Hypertriglyceridemia Secondary to Metabolic Syndrome
Authors: Meryem Abi-Ayad, Biagio Arcidiacono, Eusebio Chiefari, Daniela Foti, Mohamed Benyoucef, Antonio Brunetti
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Lipoprotein Lipase (LPL) is a key enzyme for lipid metabolism; its genetic polymorphism can be a candidate for modulating lipids parameters in metabolic syndrome. The objective of the present study was to determine whether lipoproteins lipase polymorphisMetS (LPL-HindIII) could be associated with moderate hypertriglyceridemia (secondary to metabolism syndrome). The polymorphism Hind III (rs320) was assessed by PCR-RFLP in 51 MetS patients and 17 healthy controls from the hospital in Tlemcen. The logistic regression analyses showed no significant association with Hind III genotype and hypertriglyceridemia (TG ≥ 1,5g/l or TG lower treatment) (P=0,455), metabolic syndrome (P=0,455), hypertension (P=0,802) and type 2 diabetes (P=0,144). In terms of plasma biomarkers, although not statistically significant, there was a difference in TG levels (P > 0,05), which was lowest among carriers of the homogenous mutant allele (H-). In this study, there was no association between the rare allele (H-) and disease protection, and between the frequent allele (H+) and disease prevalence (hypertriglyceridemia, metabolic syndrome, hypertension, type 2 diabetes).Keywords: moderate secondary hypertriglyceridemia, metabolic syndrome, lipids, polymorphism lipoprotein lipase, HindIII(rs320)
Procedia PDF Downloads 316583 The Effects of Applied Negative Bias Voltage on Structure and Optical Properties of a-C:H Films
Authors: X. L. Zhou, S. Tunmee, I. Toda, K. Komatsu, S. Ohshio, H. Saitoh
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Hydrogenated amorphous carbon (a-C:H) films have been synthesized by a radio frequency plasma enhanced chemical vapor deposition (rf-PECVD) technique with different bias voltage from 0.0 to -0.5 kV. The Raman spectra displayed the polymer-like hydrogenated amorphous carbon (PLCH) film with 0.0 to -0.1 and a-C:H films with -0.2 to -0.5 kV of bias voltages. The surface chemical information of all films were studied by X-ray photo electron spectroscopy (XPS) technique, presented to C-C (sp2 and sp3) and C-O bonds, and relative carbon (C) and oxygen (O) atomics contents. The O contamination had affected on structure and optical properties. The true density of PLCH and a-C:H films were characterized by X-ray refractivity (XRR) method, showed the result as in the range of 1.16-1.73 g/cm3 that depending on an increasing of bias voltage. The hardness was proportional to the true density of films. In addition, the optical properties i.e. refractive index (n) and extinction coefficient (k) of these films were determined by a spectroscopic ellipsometry (SE) method that give formation to in 1.62-2.10 (n) and 0.04-0.15 (k) respectively. These results indicated that the optical properties confirmed the Raman results as presenting the structure changed with applied bias voltage increased.Keywords: negative bias voltage, a-C:H film, oxygen contamination, optical properties
Procedia PDF Downloads 476582 Pharmacokinetics of First-Line Tuberculosis Drugs in South African Patients from Kwazulu-Natal: Effects of Pharmacogenetic Variation on Rifampicin and Isoniazid Concentrations
Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi
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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis
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