103 resultados para Algebraic path formulation
Resumo:
In this paper the evolution of a time domain dynamic identification technique based on a statistical moment approach is presented. This technique can be used in the case of structures under base random excitations in the linear state and in the non linear one. By applying Itoˆ stochastic calculus, special algebraic equations can be obtained depending on the statistical moments of the response of the system to be identified. Such equations can be used for the dynamic identification of the mechanical parameters and of the input. The above equations, differently from many techniques in the literature, show the possibility of obtaining the identification of the dissipation characteristics independently from the input. Through the paper the first formulation of this technique, applicable to non linear systems, based on the use of a restricted class of the potential models, is presented. Further a second formulation of the technique in object, applicable to each kind of linear systems and based on the use of a class of linear models, characterized by a mass proportional damping matrix, is described.
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The reaction mechanism of CO and Fe2O3 in a chemical-looping combustion (CLC) was studied based on density functional theory (DFT) at B3LYP level in this paper. The structures of all reactants, intermediate, transition structures and products of this reaction had been optimized and characterized. The reaction path was validated by means of the intrinsic reaction coordinate (IRC) approach. The result showed that the reaction was divided into two steps, the adsorbed CO molecule on Fe 2O3 surface formed a medium state with one broken Fe-O bond in step1, and in step2, O atom broken here oxidized a subsequent CO molecule in the fuel reactor. Thus, Fe2O3 molecule transport O from air to oxide CO continually in the CLC process. The activation energy and rate coefficients of the two steps were also obtained.
Resumo:
Inhaled antibiotics, such as tobramycin, for the treatment of Pseudomonas aeruginosa pulmonary infections are associated with the increase in life expectancy seen in cystic fibrosis (CF) patients over recent years. However, the effectiveness of this aminoglycoside is still limited by its inability to penetrate the thick DNA-rich mucus in the lungs of these patients, leading to low antibiotic exposure to resident bacteria. In this study, we created novel polymeric nanoparticle (NP) delivery vehicles for tobramycin. Using isothermal titration calorimetry, we showed that tobramycin binds with alginate polymer and, by exploiting this interaction, optimised the production of tobramycin alginate/chitosan NPs. It was established that NP antimicrobial activity against P. aeruginosa PA01 was equivalent to unencapsulated tobramycin (minimum inhibitory concentration 0.625 mg/L). Galleria mellonella was employed as an in vivo model for P. aeruginosa infection. Survival rates of 90% were observed following injection of NPs, inferring low NP toxicity. After infection with P. aeruginosa, we showed that a lethal inoculum was effectively cleared by tobramycin NPs in a dose dependent manner. Crucially, a treatment with NPs prior to infection provided a longer window of antibiotic protection, doubling survival rates from 40% with free tobramycin to 80% with NP treatment. Tobramycin NPs were then functionalised with dornase alfa (recombinant human deoxyribonuclease I, DNase), demonstrating DNA degradation and improved NP penetration of CF sputum. Following incubation with CF sputum, tobramycin NPs both with and without DNase functionalisation, exhibited anti-pseudomonal effects. Overall, this work demonstrates the production of effective antimicrobial NPs, which may have clinical utility as mucus-penetrating tobramycin delivery vehicles, combining two widely used CF therapeutics into a single NP formulation. This nano-antibiotic represents a strategy to overcome the mucus barrier, increase local drug concentrations, avoid systemic adverse effects and improve outcomes for pulmonary infections in CF.
Resumo:
Objectives: This article uses conventional and newly extended solubility parameter (δ) methods to identify polymeric materials capable of forming amorphous dispersions with itraconazole (itz). Methods: Combinations of itz and Soluplus, Eudragit E PO (EPO), Kollidon 17PF (17PF) or Kollidon VA64 (VA64) were prepared as amorphous solid dispersions using quench cooling and hot melt extrusion. Storage stability was evaluated under a range of conditions using differential scanning calorimetry and powder X-ray diffraction. Key findings: The rank order of itz miscibility with polymers using both conventional and novel δ-based approaches was 17PF > VA64 > Soluplus > EPO, and the application of the Flory–Huggins lattice model to itz–excipient binary systems corroborated the findings. The solid-state characterisation analyses of the formulations manufactured by melt extrusion correlated well with pre-formulation screening. Long-term storage studies showed that the physical stability of 17PF/vitamin E TPGS–itz was poor compared with Soluplus and VA64 formulations, and for EPO/itz systems variation in stability may be observed depending on the preparation method. Conclusion: Results have demonstrated that although δ-based screening may be useful in predicting the initial state of amorphous solid dispersions, assessment of the physical behaviour of the formulations at relevant temperatures may be more appropriate for the successful development of commercially acceptable amorphous drug products.
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The singlet excited state of the 4-aminonaphthalimide fluorophore in 1a and 1b directs electron transfer from intramolecular but external amine groups along only one of two available paths.
Resumo:
Objectives: Amorphous drug forms provide a useful method of enhancing the dissolution performance of poorly water-soluble drugs; however, they are inherently unstable. In this article, we have used Flory–Huggins theory to predict drug solubility and miscibility in polymer candidates, and used this information to compare spray drying and melt extrusion as processes to manufacture solid dispersions.
Method: Solid dispersions were characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry) and spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods.
Key Findings: Spray drying permitted generation of amorphous solid dispersions to be produced across a wider drug concentration than melt extrusion. Melt extrusion provided sufficient energy for more intimate mixing to be achieved between drug and polymer, which may improve physical stability. It was also confirmed that stronger drug–polymer interactions might be generated through melt extrusion. Remixing and dissolution of recrystallised felodipine into the polymeric matrices did occur during the modulated differential scanning calorimetry analysis, but the complementary information provided from FTIR confirms that all freshly prepared spray-dried samples were amorphous with the existence of amorphous drug domains within high drug-loaded samples.
Conclusion: Using temperature–composition phase diagrams to probe the relevance of temperature and drug composition in specific polymer candidates facilitates polymer screening for the purpose of formulating solid dispersions.
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We pursue a comparative analysis of employers’ age management practices in Britain and Germany, asking how valid ‘convergence’ and ‘Varieties of Capitalism’ theories are. After rejecting the convergence verdict, we proceed to ask how far ‘path dependence’ helps explain inter-country differences. Through 19 interviews with British and German experts, we find that firms have reacted in different ways to promptings from the EU and the two states. Change has been modest and a rhetoric-reality gap exists in firms as they seek to hedge. We point to continuities in German institutional methods of developing new initiatives, and the emerging role of British NGOs in helping firms and the state develop new options. We argue that ‘path dependence’ offers insight into the national comparison, but also advance the idea of national modes of firm optionexploration as an important way of conceptualizing the processes involved.