Investigation of the Antiviral Activity of Triterpenoid Compounds Against Retoviruses

The triterpenoid compound glycyrrhizin (GL) is widely used in Japan for the treatment of viral hepatitis. GL, carbenoxolone sodium (CBX), and cicloxolone sodium (CCX) exhibit broad range antiviral activity both in vivo and in vitro. Both in vitro and in vivo anti-HIV activity has also been reported for GL. This thesis investigates the effect of triterpenoid compounds on replication of two retrovirus in tissue cultures; Feline leukaemia virus type A (FeLV-A) and Feline immunodeficiency virus (FIV). Both of these viruses cause AIDS-like immunodeficiency diseases in cats. The anti-retrovirus activity of the triterpenoid compounds is contrasted with the effect of the drugs on the replication of bovine herpesvirus type 1 (BHV-1) in MDBK cells. Triterpenoid compounds are lipophilic and effect the host cell membrane functions. In order to determine drug concentrations in which cytotoxic effect of the drug could be uncoupled from the antiviral activity, cyotoxicity tests were performed. The effect of the drugs on cell culture growth and percentage cell viability were determined by trypan blue dye exclusion. The highest drug concentrations tolerated were; for FeA and CrFK cells 100muM CCX, or 100muM CBX and for MDBK cells 300muM CCX (used for BHV-1 studies). Drug removal experiments have shown that the effect of the drugs was reversible and that two days treatment with 100muM CCX, or 100muM CBX had no effect on the subsequent growth of FeA or CrFK cell cultures. The IC50 concentrations (concentration of the drug inhibiting cellular growth by 50%) determined for both CrFK and FeA cells after 24h or 48h drug treatments were > 300muM and 150muM respectively. Based on the data obtained from cytotoxicity tests, it was concluded that CrFK and FeA cells could be placed within the grouping of CCX-resistant cell lines classified by Galt et al., (1990). In order, to investigate the intracellular location of CCX molecules, an attempt was made to generate an anti-CCX antibody in immunise rabbits. Despite detection of an apparent anti-CCX antibody in an ELISA test, experiments designed to demonstrate the specific antibody tagging of CCX molecules in drug treated cells by immunofluorescence were unsuccessful. Previous studies have shown that CCX treatment impaired the glycosylation of HSV, VSV, and SFV glycoproteins, suggesting that the Golgi apparatus might be a target for triterpenoid compounds. A trans-Golgi specific monoclonal antibody (directed against the p58 protein) was employed to investigate the effect of CCX on the MDBK and CrFK cells Golgi apparatus. While perinuclear (Golgi) immunofluorescence was observed in drugfree cultures, little or no such staining was detected in cells treated with CCX, suggesting that the drug perturb the Golgi apparatus. It was further postulated that up-regulation of Na+/K+ATPase activity (a known effect of triterpenoid compounds) might play a role in the effect of CCX on the Golgi apparatus. To test this hypothesis, ouabain (a specific inhibitor of Na+/K+ATPase activity) was used in Golgi immunofluorescence labelling experiments. The effect of CCX on the Golgi apparatus of MDBK cells was impaired when cells were pre-treated with ouabain, confirming that the CCX-induced perturbation of the trans-Golgi compartment was associated with the up-regulation of Na+/K+ATPase activity. A model that can explain the effect of the triterpenoid compounds on Golgi apparatus has been given. CBX and GL exhibit mild virucidal activity against FeLV-A, FIV, and BHV-1. 300muM CCX treatment of virus particles in suspensions resulted in a 4 fold reduction in FeLV-A, and 10 fold reduction of FIV infectivity. Treatment of BHV-1 particles with 1500muM GL resulted in a 4.2 fold reduction infectivity. FeLV-A infectious virus yield, drug-dose-response experiments in which infected FeA cells were treated with increasing concentrations of CCX, CBX, or GL resulted in extracellular reductions of 155, 101, and 128 fold, when treated with 150muM CCX, 150muM CBX, or 2500muM GL respectively. The kinetics of the dose-response curves obtained for each drug were triphasic; an initial ~ 10 fold reduction in infectivity when cells were treated with 25muM CCX, 25muM CBX, or 500muM GL, followed by a near plateau in the curve up to 100muM CCX, 100muM CBX or 2000muM GL, and a sharp decrease in the curve at 150muM CCX, 150muM CBX, or 2500muM GL. The results suggest that the antiviral activity of triterpenoid compounds may operate by inhibiting two different target functions; the first, a function that enhances but is not essential for virus infectivity and which is sensitive to low drug concentrations, and the second, a function which is probably essential for virus replication and which is only sensitive to high concentrations of the drugs. (Abstract shortened by ProQuest.)

Automated scheduling of hostel room allocation using genetic algorithm

Due to the rapid growth of the student population in tertiary institutions in many developing countries, hostel space has become one of the most important resources in university. Therefore, the decision of student selection and hostel room allocation is indeed a critical issue for university administration. This paper proposes a hierarchical heuristics approach to cope with hostel room allocation problem. The proposed approach involves selecting eligible students using rank based selection method and allocating selected students to the most suitable hostel room possible via the implementation of a genetic algorithm (GA). We also have examined the effects of using different weight associated with constraints on the performance of the GA. Results obtained from the experiments illustrate the feasibility of the suggested approach in solving the hostel room allocation problem

Bio-efficacy of hydroxy-selenomethionine as a selenium supplement in pregnant dairy heifers and on the selenium status of their calves

This study aimed to determine the effects of supplementing pregnant heifers with the organic selenium source 2-hydroxy-4-methylselenobutanoic acid (HMSeBA) during last eight weeks of pregnancy on dam and calf Se status. A total of 42 in-calf heifers were recruited to the study and randomly allocated to one of three treatments; a negative control (Con), sodium selenite (NaSe) or HMSeBA. Animals were blocked by body weight, body condition score, and expected calving date prior to treatment allocation. Following enrollment all animals underwent a seven week wash-out period after which they received their respective supplements, topped dressed daily onto a basal diet for the last eight weeks of pregnancy. Heifer blood samples were taken at weekly intervals from enrollment until two weeks before expected calving date, and as soon as possible after calving for determination of whole blood glutathione peroxidase activity (GSH-Px) and plasma selenium (Se) and malondealdehyde (MDA) concentrations. Selenized amino acids were determined in plasma samples taken at three weeks pre-calving. A colostrum sample was taken as close to parturition as possible for determination of colostrum total Se, selenized amino acid, and Immunoglobulin G (IgG) concentration. Calves were blood sampled as close to birth as possible for determination of whole blood GSH-Px activity and plasma Se and MDA concentration. Differences in whole blood GSH-Px activity did not become apparent until calving; GSH-Px activity was lowest in Con heifers (P < 0.05) but similar between NaSe and HMSeBA. Plasma Se was lowest in unsupplemented heifers and greatest in those supplemented with HMSeBA (P < 0.001) and this was attributable to greater selenomethionine concentrations in the plasma of HMSeBA heifers (P < 0.01). Colostrum Se was lowest in Con heifers and greatest in HMSeBA (P < 0.001), the greater Se concentration of HMSeBA heifers was attributable to a greater proportion of total Se comprising selenocysteine (P = 0.061), the reason for this is not known. There was no effect of supplementation on colostrum IgG concentration. Plasma Se was lowest in those calves born to Con heifers and greatest in those born to HMSeBA heifers (P < 0.001). There were no effects of treatment on calf whole blood GSH-Px activity or plasma MDA concentration. The enhanced Se status associated with HMSeBA supplementation is likely a consequence of selenomethionine supply and may confer benefits to both the dam and her calf post-partum

A Pre-Process Enhanced Digital Image Correlation Approach for Smart Structure Monitoring

This research provides a practical guideline for Digital Image Correlation (DIC) data variations minimization in structural engineering through simple image processing techniques. The main objective of this research is to investigate the Pixel Averaging (P.A.) effect on the differential strain Diff(εx) variations. Three concrete arches were tested with three-point bending using the DIC technique for strain measurements. The measured strains are obtained through two virtual horizontal extensometers in the middle of each arch. The Diff(εx) was selected to avoid other 2D-DIC issues, such as the sample-camera out-of-plane movement. Three image cases, namely, one, ten, and twenty averaged images, were used for DIC analysis of each arch. The conditions of each image case are assessed by computing the Diff(εx) variance and the linear least square criterion (R2) between the two extensometers. The second objective is to examine the speckles’ dilation effects on the speckle pattern density and surface component quality utilizing the Image Erode (I.E.) technique. The (P.A.) technique provided consistent differential strain Diff(εx) values with a variance reduction of up to (90%) when averaged images were used. The (R2) has considerably increased (from 0.46, 0.66, 0.91 to 0.90, 0.96, 0.99), respectively, for the three samples. Moreover, the (I.E.) technique provided qualitatively denser speckles with a highly consistent DIC surface component

A Pre-Process Enhanced Digital Image Correlation Approach for Smart Structure Monitoring

This research provides a practical guideline for Digital Image Correlation (DIC) data variations minimization in structural engineering through simple image processing techniques. The main objective of this research is to investigate the Pixel Averaging (P.A.) effect on the differential strain Diff(&epsilon;x) variations. Three concrete arches were tested with three-point bending using the DIC technique for strain measurements. The measured strains are obtained through two virtual horizontal extensometers in the middle of each arch. The Diff(&epsilon;x) was selected to avoid other 2D-DIC issues, such as the sample-camera out-of-plane movement. Three image cases, namely, one, ten, and twenty averaged images, were used for DIC analysis of each arch. The conditions of each image case are assessed by computing the Diff(&epsilon;x) variance and the linear least square criterion (R2) between the two extensometers. The second objective is to examine the speckles&rsquo; dilation effects on the speckle pattern density and surface component quality utilizing the Image Erode (I.E.) technique. The (P.A.) technique provided consistent differential strain Diff(&epsilon;x) values with a variance reduction of up to (90%) when averaged images were used. The (R2) has considerably increased (from 0.46, 0.66, 0.91 to 0.90, 0.96, 0.99), respectively, for the three samples. Moreover, the (I.E.) technique provided qualitatively denser speckles with a highly consistent DIC surface component

Genetic stability of in vitro multiplied Phalaenopsis gigantea protocorm-like bodies as affected by chitosan

Chitosan is a carbohydrate polymer derivative of chitin which presents in shell of crustaceans. This biopolymer is a non toxic and environmentally friendly, considered as a plant growth stimulator in some plant species. The present study investigates the effects of chitosan and media types on multiplication and genetic stability of Phalaenopsis gigantea protocorm-like bodies (PLBs). PLBs were inoculated in liquid New Dogashima Medium (NDM) and Vacin and Went (VW) supplemented with various concentrations of chitosan (0, 5, 10, 15, 20 and 25 mg/L). The highest PLB multiplication was observed on VW and NDM supplemented with 10 mg/L chitosan with mean number of PLBs 177 and 147, respectively. Chitosan promoted the formation of juvenile leaves and the highest number was observed in NDM supplemented with 20 mg/L chitosan with mean number of 66 leaves after 8 weeks of culture. Genetic stability was assessed among mother plant and secondary PLBs after 2, 4, 6, and 8 weeks of culture in liquid media. 8 out of 10 ISSR markers produced a total of 275 clear and reproducible bands with mean of 6.9 bands per primer. The secondary PLBs produced during sub-culturing process of chitosan treated liquid culture were genetically uniform and similar to mother plant

An archive-based multi-objective arithmetic optimization algorithm for solving industrial engineering problems

This research proposes an Archive-based Multi-Objective Arithmetic Optimization Algorithm (MAOA) as an alternative to the recently established Arithmetic Optimization Algorithm (AOA) for multi-objective problems (MAOA). The original AOA approach was based on the distribution behavior of vital mathematical arithmetic operators, such as multiplication, division, subtraction, and addition. The idea of the archive is introduced in MAOA, and it may be used to find non-dominated Pareto optimum solutions. The proposed method is tested on seven benchmark functions, ten CEC-2020 mathematic functions, and eight restricted engineering design challenges to determine its suitability for solving real-world engineering difficulties. The experimental findings are compared to five multi-objective optimization methods (Multi-Objective Particle Swarm Optimization (MOPSO), Multi-Objective Slap Swarm Algorithm (MSSA), Multi-Objective Ant Lion Optimizer (MOALO), Multi-Objective Genetic Algorithm (NSGA2) and Multi-Objective Grey Wolf Optimizer (MOGWO) reported in the literature using multiple performance measures. The empirical results show that the proposed MAOA outperforms existing state-of-the-art multi-objective approaches and has a high convergence rate.Web of Science1010669810667

A Distributed Bi-Behaviors Crow Search Algorithm for Dynamic Multi-Objective Optimization and Many-Objective Optimization Problems

Dynamic Multi-Objective Optimization Problems (DMOPs) and Many-Objective Optimization Problems (MaOPs) are two classes of the optimization field that have potential applications in engineering. Modified Multi-Objective Evolutionary Algorithms hybrid approaches seem to be suitable to effectively deal with such problems. However, the standard Crow Search Algorithm has not been considered for either DMOPs or MaOPs to date. This paper proposes a Distributed Bi-behaviors Crow Search Algorithm (DB-CSA) with two different mechanisms, one corresponding to the search behavior and another to the exploitative behavior with a dynamic switch mechanism. The bi-behaviors CSA chasing profile is defined based on a large Gaussian-like Beta-1 function, which ensures diversity enhancement, while the narrow Gaussian Beta-2 function is used to improve the solution tuning and convergence behavior. Two variants of the proposed DB-CSA approach are developed: the first variant is used to solve a set of MaOPs with 2, 3, 5, 7, 8, 10,15 objectives, and the second aims to solve several types of DMOPs with different time-varying Pareto optimal sets and a Pareto optimal front. The second variant of DB-CSA algorithm (DB-CSA-II) is proposed to solve DMOPs, including a dynamic optimization process to effectively detect and react to the dynamic change. The Inverted General Distance, the Mean Inverted General Distance and the Hypervolume Difference are the main measurement metrics used to compare the DB-CSA approach to the state-of-the-art MOEAs. The Taguchi method has been used to manage the meta-parameters of the DB-CSA algorithm. All quantitative results are analyzed using the non-parametric Wilcoxon signed rank test with 0.05 significance level, which validated the efficiency of the proposed method for solving 44 test beds (21 DMOPs and 23 MaOPS)