| 1. |
- Blanch, Ewan W, et al.
(author)
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Is polyproline II helix the killer conformation? A Raman optical activity study of the amyloidogenic prefibrillar intermediate of human lysozyme.
- 2000
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In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 301:2, s. 553-563
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Journal article (peer-reviewed)abstract
- The amyloidogenic prefibrillar partially denatured intermediate of human lysozyme, prepared by heating the native protein to 57 degrees C at pH 2.0, was studied using Raman optical activity (ROA). A positive band in the room temperature ROA spectrum of the native protein at approximately 1345 cm(-1), assigned to a hydrated form of alpha-helix, is not present in that of the prefibrillar intermediate, where a new strong positive band at approximately 1318 cm(-1) appears instead that is assigned to the poly(l-proline) II (PPII)-helical conformation. A sharp negative band at approximately 1241 cm(-1) in the native protein, assigned to beta-strand, shows little change in the ROA spectrum of the prefibrillar intermediate. The disappearance of a positive ROA band at approximately 1551 cm(-1) assigned to vibrations of tryptophan side-chains indicates that major conformational changes have occurred among the five tryptophan residues present in human lysozyme, four of which are located in the alpha-domain. The various ROA data suggest that a substantial loss of tertiary structure has occurred in the prefibrillar intermediate and that this is located more in the alpha-domain than in the beta-domain. There is no evidence for any increase in beta-structure. The ROA spectrum of hen lysozyme, which does not form amyloid fibrils so readily, remains much more native-like on heating to 57 degrees C at pH 2.0. The thermal behaviour of the alanine-rich alpha-helical peptide AK21 in aqueous solution was found to be similar to that of human lysozyme. Hydrated alpha-helix therefore appears to readily undergo a conformational change to PPII structure on heating, which may be a key step in the conversion of alpha-helix into beta-sheet in the formation of amyloid fibrils in human lysozyme. Since it is extended, flexible, lacks intrachain hydrogen bonds and is fully hydrated in aqueous solution, PPII helix has the appropriate characteristics to be implicated as a critical conformational element in many conformational diseases. Disorder of the PPII type may be a sine qua non for the formation of regular fibrils; whereas the more dynamic disorder of the random coil may lead only to amorphous aggregates.
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| 2. |
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| 3. |
- Gautschi, Nicolas, et al.
(author)
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Rapid determination of drug solubilization versus supersaturation in natural and digested lipids
- 2016
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 513:1-2, s. 164-174
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Journal article (peer-reviewed)abstract
- Lipid-based formulations (LBFs) represent one of the successful formulation approaches that enable oral delivery of poorly water-soluble drugs. This work presents a simple equilibrium approach based on solubility in lipids and their corresponding digestion media to estimate a maximum drug supersaturation ratio (SRmax). This value of drug concentration normalized by the solubility in the aqueous digestion phase indicates the propensity for drug precipitation. A set of 16 structurally diverse drugs was first measured for their solubility in tricaprin and tricaprylin and results were compared to an empirical model based on molecular predictors. In the next step, digestion media were either prepared by in vitro lipolysis or by assembling a composition to mimic the endpoint of digestion. It was found that drug solubility in the pure lipids mainly was related to the melting point in that increased values resulted in reduced solubility. The solubility values measured in the lipolysis media correlated well with those obtained from assembled digestion media. Interestingly, the solubilization upon digestion was typically higher when using tricaprin than tricaprylin in spite of that the latter oil (as pure excipient) generally was a more potent solvent. This work suggests that a simplified digestion screen can be used to facilitate evaluation of formulations during early development. Estimation of SRmax provides an early risk assessment of drug precipitation for LBFs. The method is easily scaled down to the microtiter plate format and can be used for selecting candidate formulations that merit further evaluation in more complex and dynamic in vitro tests.
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| 4. |
- Gautschy-Loidl, Rita, et al.
(author)
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Dynamic model atmospheres of AGB stars : IV. A comparison of synthetic carbon star spectra with observations
- 2004
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 422, s. 289-306
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Journal article (peer-reviewed)abstract
- We have calculated synthetic opacity sampling spectra for carbon-rich Asymptotic Giant Branch (AGB) stars based on dynamic model atmospheres which couple time-dependent dynamics and frequency-dependent radiative transfer, as presented in the third paper of this series. We include the molecules CO, CH, CN, C2, CS, HCN, C2H2 and C3 in our calculations, both when computing the atmospheric structures, and the synthetic spectra. A comparison of the synthetic spectra with various observed colours and spectra in the wavelength range between 0.5 and 25 μm,of TX Psc, WZ Cas, V460 Cyg, T Lyr and S Cep is presented. We obtain good agreement between observations gathered at different phases and synthetic spectra of one single hydrodynamical model for each star in the wavelength region between 0.5 and 5 μm. At longer wavelengths our models showing mass loss offer a first self-consistent qualitative explanation of why a strong feature around 14 μm, which is predicted by all hydrostatic models as well as dynamical models showing no mass loss, is missing in observed AGB carbon star spectra.
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| 5. |
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| 6. |
- Montero Villar, Gonzalo, 1992, et al.
(author)
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Investigation of Phase-Lagged Boundary Conditions for Turbulence Resolving Turbomachinery Simulations
- 2020
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In: AIAA AVIATION 2020 FORUM. - Reston, Virginia : American Institute of Aeronautics and Astronautics. ; 1
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Conference paper (peer-reviewed)abstract
- The present work explores whether phase-lagged boundary conditions can be used to perform scale resolving simulations of turbomachines. The phase-lagged approach considered is based on storing the flow signal, both at the pitch-wise boundaries and the rotor-stator interface, as its temporal Fourier coefficients for a finite number of harmonics. The method is implemented in an in-house CFD solver, G3D::Flow, which can perform both URANS and hybrid RANS/LES simulations. In order to evaluate the performance of the phase-lagged boundary condition, a comparison is made with a sliding mesh simulation on a compressor cascade. Furthermore, the possibility of breaking an error feedback loop generated in the sampling process by including multiple blade passages is also investigated. It is found that this approach greatly improves convergence and accuracy of the sampling.
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| 7. |
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| 8. |
- Pugh, RJ
(author)
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Surface chemical analysis of oxidized α-SiC powders by electron spectroscopy
- 1990
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In: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 138, s. 16-20
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Journal article (peer-reviewed)abstract
- The oxidation behavior of ultrafine α-SiC powder was studied in air at temperatures up to 1100°C. The thickness of the oxidized film that formed was determined by electron spectroscopy for chemical analysis at a range of oxidation times and from this data the oxidation rates were calculated. From an Arrhenius plot a relatively low value (≈45 kJ/mol) for the apparent activation energy was obtained for the initial stages of the oxidation process. This value appears to support the mechanism involving the diffusion of oxidant species through the surface film.
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| 9. |
- Pugh, Rhiannon, et al.
(author)
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Taking the systems approaches out of their comfort zones: Perspectives from under explored contexts
- 2021
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In: Growth and Change. - : Wiley. - 0017-4815 .- 1468-2257. ; 52:2, s. 608-620
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Journal article (peer-reviewed)abstract
- This special issue tackles two “trendy” topics much discussed at present by the community of scholars (and practitioners too) interested in regional economic development: systems and ecosystems. These metaphors have proved popular, and enduring, currently experiencing something of a buzz or moment in the sunshine. This special issue pushes them out of their comfort zone to explore contexts, elements, and approaches that have not yet been well explored in the literature to date. Contributions in this special issue cover a wide range of international cases and explore systemic perspectives on economic development placing institutional context and evolutionary dynamics at the core.
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| 10. |
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