A preliminary investigation into the impact of a pesticide combination on human neuronal and glial cell lines in vitro

Many pesticides are used increasingly in combinations during crop protection and their stability ensures the presence of such combinations in foodstuffs. The effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were investigated together and separately on U251 and SH-SY5Y cells, which can be representative of human CNS glial and neuronal cells respectively. Over 48h, all three agents showed significant reductions in cellular ATP, at concentrations that were more than tenfold lower than those which significantly impaired cellular viability. The effects on energy metabolism were reflected in their marked toxic effects on mitochondrial membrane potential. In addition, evidence of oxidative stress was seen in terms of a fall in cellular thiols coupled with increases in the expression of enzymes associated with reactive species formation, such as GSH peroxidase and superoxide dismutase. The glial cell line showed significant responsiveness to the toxin challenge in terms of changes in antioxidant gene expression, although the neuronal SH-SY5Y line exhibited greater vulnerability to toxicity, which was reflected in significant increases in caspase-3 expression, which is indicative of the initiation of apoptosis. Cyprodinil was the most toxic agent individually, although oxidative stress-related enzyme gene expression increases appeared to demonstrate some degree of synergy in the presence of the combination of agents. This report suggests that the impact of some pesticides, both individually and in combinations, merits further study in terms of their impact on human cellular health.

Manipulation of the surface pegylation in combination with reduced vesicle size of cationic liposomal adjuvants modifies their clearance kinetics from the injection site, and the rate and type of T cell response

The mechanism behind the immunostimulatory effect of the cationic liposomal vaccine adjuvant dimethyldioctadecylammonium and trehalose 6,6′- dibehenate (DDA:TDB) has been linked to the ability of these cationic vesicles to promote a depot after administration, with the liposomal adjuvant and the antigen both being retained at the injection site. This can be attributed to their cationic nature, since reduction in vesicle size does not influence their distribution profile yet neutral or anionic liposomes have more rapid clearance rates. Therefore the aim of this study was to investigate the impact of a combination of reduced vesicle size and surface pegylation on the biodistribution and adjuvanticity of the formulations, in a bid to further manipulate the pharmacokinetic profiles of these adjuvants. From the biodistribution studies, it was found that with small unilamellar vesicles (SUVs), 10% PEGylation of the formulation could influence liposome retention at the injection site after 4 days, whilst higher levels (25 mol%) of PEG blocked the formation of a depot and promote clearance to the draining lymph nodes. Interestingly, whilst the use of 10% PEG in the small unilamellar vesicles did not block the formation of a depot at the site of injection, it did result in earlier antibody response rates and switch the type of T cell responses from a Th1 to a Th2 bias suggesting that the presence of PEG in the formulation not only control the biodistribution of the vaccine, but also results in different types of interactions with innate immune cells. © 2012 Elsevier B.V.

Investigation of formulation and process of lyophilised orally disintegrating tablet (ODT) using novel amino acid combination

Lyophilised orally disintegrating tablets (ODTs) have achieved a great success in overcoming dysphagia associated with conventional solid dosage forms. However, the extensive use of saccharides within the formulation limits their use in treatment of chronic illnesses. The current study demonstrates the feasibility of using combination of proline and serine to formulate zero sacharide ODTs and investigates the effect of freezing protocol on sublimation rate and tablets characteristics. The results showed that inclusion of proline and serine improved ODT properties when compared to individual counterparts. Additionally, annealing the ODTs facilitated the sublimation process and shortened the disintegration time. © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

An investigation into the formation of wax emulsion

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The development of a wax layer on the interior wall of a circular pipe transporting heated oil

In this article we develop a simple model to describe the evolution of a depositional wax layer on the inner surface of a circular pipe transporting heated oil, which contains dissolved wax. When the outer pipe surface is cooled sufficiently, the growth of a wax layer is initiated on the inner pipe wall, and this evolves to a saturated steady state thickness. The model proposed is based on fundamental balances of heat flow from the oil, into the wax layer, and across the pipe wall. We present an analysis of the model, examine a relevant asymptotic limit in which the full details of the solution to the model are available and develop an efficient numerical method (based on the method of fundamental solutions) for producing approximations of the model solution. The mathematical structure of the model is that of a free boundary evolution problem of generalised Stefan type. © The Author, 2014.

The development of a wax layer on the interior wall of a circular pipe transporting heated oil

In this article we develop a simple model to describe the evolution of a depositional wax layer on the inner surface of a circular pipe transporting heated oil, which contains dissolved wax. When the outer pipe surface is cooled sufficiently, the growth of a wax layer is initiated on the inner pipe wall, and this evolves to a saturated steady state thickness. The model proposed is based on fundamental balances of heat flow from the oil, into the wax layer, and across the pipe wall. We present an analysis of the model, examine a relevant asymptotic limit in which the full details of the solution to the model are available and develop an efficient numerical method (based on the method of fundamental solutions) for producing approximations of the model solution. The mathematical structure of the model is that of a free boundary evolution problem of generalised Stefan type. © The Author, 2014.

Personal knowledge development in online learning:a model for measuring externalisation, combination and internalisation

This paper presents a model for measuring personal knowledge development in online learning environments. It is based on Nonaka‘s SECI model of organisational knowledge creation. It is argued that Socialisation is not a relevant mode in the context of online learning and was therefore not covered in the measurement instrument. Therefore, the remaining three of SECI‘s knowledge conversion modes, namely Externalisation, Combination, and Internalisation were used and a measurement instrument was created which also examines the interrelationships between the three modes. Data was collected using an online survey, in which online learners report on their experiences of personal knowledge development in online learning environments. In other words, the instrument measures the magnitude of online learners‘ Externalisation and combination activities as well as their level of internalisation, which is the outcome of their personal knowledge development in online learning.

Detection of organic aromatic compounds in paraffin by a long-period fiber grating optical sensor with optimized sensitivity

A long-period grating (LPG) sensor is used to detect small variations in the concentration of an organic aromatic compound (xylene) in a paraffin (heptane) solution. A new design procedure is adopted and demonstrated to maximize the sensitivity of LPG (wavelength shift for a change in the surrounding refractive index, (dλ/dn3)) for a given application. The detection method adopted is comparable to the standard technique used in industry (high performance liquid chromatograph and UV spectroscopy) which has a relative accuracy between ∼±0.5% and 5%. The minimum detectable change in volumetric concentration is 0.04% in a binary fluid with the detection system presented. This change of concentration relates to a change in refractive index of Δn ∼ 6 × 10-5. © 2001 Elsevier Science B.V.

Class I T-cell epitope prediction:improvements using a combination of proteasome cleavage, TAP affinity, and MHC binding

Cleavage by the proteasome is responsible for generating the C terminus of T-cell epitopes. Modeling the process of proteasome cleavage as part of a multi-step algorithm for T-cell epitope prediction will reduce the number of non-binders and increase the overall accuracy of the predictive algorithm. Quantitative matrix-based models for prediction of the proteasome cleavage sites in a protein were developed using a training set of 489 naturally processed T-cell epitopes (nonamer peptides) associated with HLA-A and HLA-B molecules. The models were validated using an external test set of 227 T-cell epitopes. The performance of the models was good, identifying 76% of the C-termini correctly. The best model of proteasome cleavage was incorporated as the first step in a three-step algorithm for T-cell epitope prediction, where subsequent steps predicted TAP affinity and MHC binding using previously derived models.

A preliminary evaluation of a novel method to monitor a triple antioxidant combination (vitamins E, C and alpha-lipoic acid) in diabetic volunteers using in vitro methaemoglobin formation

Eight otherwise healthy diabetic volunteers took a daily antioxidant supplement consisting of vitamin E (200 IU), vitamin C (250 mg) and α-lipoic acid (90 mg) for a period of 6 weeks. Diabetic dapsone hydroxylamine-mediated methaemoglobin formation and resistance to erythrocytic thiol depletion was compared with age and sex-matched non-diabetic subjects. At time zero, methaemoglobin formation in the non-diabetic subjects was greater at all four time points compared with that of the diabetic subjects. Resistance to glutathione depletion was initially greater in non-diabetic compared with diabetic samples. Half-way through the study (3 weeks), there were no differences between the two groups in methaemoglobin formation and thiol depletion in the diabetic samples was now lower than the non-diabetic samples at 10 and 20 min. At 6 weeks, diabetic erythrocytic thiol levels remained greater than those of non-diabetics. HbA1c values were significantly reduced in the diabetic subjects at 6 weeks compared with time zero values. At 10 weeks, 4 weeks after the end of supplementation, the diabetic HbA1c values significantly increased to the point where they were not significantly different from the time zero values. Total antioxidant status measurement (TAS) indicated that diabetic plasma antioxidant capacity was significantly improved during antioxidant supplementation. Conversion of α-lipoic acid to dihydrolipoic acid (DHLA) in vivo led to potent interference in a standard fructosamine assay kit, negating its use in this study. This report suggests that triple antioxidant therapy in diabetic volunteers attenuates the in vitro experimental oxidative stress of methaemoglobin formation and reduces haemoglobin glycation in vivo. © 2003 Elsevier Science B.V. All rights reserved.

An improved conflicting evidence combination approach based on a new supporting probability distance

To avoid counter-intuitive result of classical Dempster's combination rule when dealing with highly conflict information, many improved combination methods have been developed through modifying the basic probability assignments (BPAs) of bodies of evidence (BOEs) by using a certain measure of the degree of conflict or uncertain information, such as Jousselme's distance, the pignistic probability distance and the ambiguity measure. However, if BOEs contain some non-singleton elements and the differences among their BPAs are larger than 0.5, the current conflict measure methods have limitations in describing the interrelationship among the conflict BOEs and may even lead to wrong combination results. In order to solve this problem, a new distance function, which is called supporting probability distance, is proposed to characterize the differences among BOEs. With the new distance, the information of how much a focal element is supported by the other focal elements in BOEs can be given. Also, a new combination rule based on the supporting probability distance is proposed for the combination of the conflicting evidences. The credibility and the discounting factor of each BOE are generated by the supporting probability distance and the weighted BOEs are combined directly using Dempster's rules. Analytical results of numerical examples show that the new distance has a better capability of describing the interrelationships among BOEs, especially for the highly conflicting BOEs containing non-singleton elements and the proposed new combination method has better applicability and effectiveness compared with the existing methods.

Linear binocular combination of responses to contrast modulation:contrast-weighted summation in first- and second-order vision

Binocular combination for first-order (luminancedefined) stimuli has been widely studied, but we know rather little about this binocular process for spatial modulations of contrast (second-order stimuli). We used phase-matching and amplitude-matching tasks to assess binocular combination of second-order phase and modulation depth simultaneously. With fixed modulation in one eye, we found that binocularly perceived phase was shifted, and perceived amplitude increased almost linearly as modulation depth in the other eye increased. At larger disparities, the phase shift was larger and the amplitude change was smaller. The degree of interocular correlation of the carriers had no influence. These results can be explained by an initial extraction of the contrast envelopes before binocular combination (consistent with the lack of dependence on carrier correlation) followed by a weighted linear summation of second-order modulations in which the weights (gains) for each eye are driven by the first-order carrier contrasts as previously found for first-order binocular combination. Perceived modulation depth fell markedly with increasing phase disparity unlike previous findings that perceived first-order contrast was almost independent of phase disparity. We present a simple revision to a widely used interocular gain-control theory that unifies first- and second-order binocular summation with a single principle-contrast-weighted summation-and we further elaborate the model for first-order combination. Conclusion: Second-order combination is controlled by first-order contrast.

Combination of Global and Local Attributional Similarities for Synonym Detection

2000 Mathematics Subject Classification: 68T50.

On Supra-Bayesian Weighted Combination of Available Data Determined by Kerridge Inaccuracy and Entropy

2010 Mathematics Subject Classification: 94A17.

Optimal combination of energy crops under different policy scenarios:the case of Northern Greece

Energy crops production is considered as environmentally benign and socially acceptable, offering ecological benefits over fossil fuels through their contribution to the reduction of greenhouse gases and acidifying emissions. Energy crops are subjected to persistent policy support by the EU, despite their limited or even marginally negative impact on the greenhouse effect. The present study endeavors to optimize the agricultural income generated by energy crops in a remote and disadvantageous region, with the assistance of linear programming. The optimization concerns the income created from soybean, sunflower (proxy for energy crop), and corn. Different policy scenarios imposed restrictions on the value of the subsidies as a proxy for EU policy tools, the value of inputs (costs of capital and labor) and different irrigation conditions. The results indicate that the area and the imports per energy crop remain unchanged, independently of the policy scenario enacted. Furthermore, corn cultivation contributes the most to iFncome maximization, whereas the implemented CAP policy plays an incremental role in uptaking an energy crop. A key implication is that alternative forms of motivation should be provided to the farmers beyond the financial ones in order the extensive use of energy crops to be achieved.