Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilizing phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localized effects and relatively few studies showing transdermal delivery effects. Shortly after this, Transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial with diverse processes being reported. Parallel to this development, other classes of vesicles were produced with ethanol being included into the vesicles to provide flexibility (as in ethosomes) and vesicles were constructed from surfactants and cholesterol (as in niosomes). Thee ultradeformable vesicles showed variable efficiency in delivering low molecular weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs considering both their efficacy and potential mechanisms of action.

Consistent approximate models of the global atmosphere: shallow, deep, hydrostatic, quasi-hydrostatic and non-hydrostatic

We study global atmosphere models that are at least as accurate as the hydrostatic primitive equations (HPEs), reviewing known results and reporting some new ones. The HPEs make spherical geopotential and shallow atmosphere approximations in addition to the hydrostatic approximation. As is well known, a consistent application of the shallow atmosphere approximation requires omission of those Coriolis terms that vary as the cosine of latitude and of certain other terms in the components of the momentum equation. An approximate model is here regarded as consistent if it formally preserves conservation principles for axial angular momentum, energy and potential vorticity, and (following R. Müller) if its momentum component equations have Lagrange's form. Within these criteria, four consistent approximate global models, including the HPEs themselves, are identified in a height-coordinate framework. The four models, each of which includes the spherical geopotential approximation, correspond to whether the shallow atmosphere and hydrostatic (or quasi-hydrostatic) approximations are individually made or not made. Restrictions on representing the spatial variation of apparent gravity occur. Solution methods and the situation in a pressure-coordinate framework are discussed. © Crown copyright 2005.

The quasi-nondispersive regimes of long extratropical baroclinic rossby waves over (slowly varying) topography

Actual energy paths of long, extratropical baroclinic Rossby waves in the ocean are difficult to describe simply because they depend on the meridional-wavenumber-to-zonal-wavenumber ratio tau, a quantity that is difficult to estimate both observationally and theoretically. This paper shows, however, that this dependence is actually weak over any interval in which the zonal phase speed varies approximately linearly with tau, in which case the propagation becomes quasi-nondispersive (QND) and describable at leading order in terms of environmental conditions (i.e., topography and stratification) alone. As an example, the purely topographic case is shown to possess three main kinds of QND ray paths. The first is a topographic regime in which the rays follow approximately the contours f/h(alpha c) = a constant (alpha(c) is a near constant fixed by the strength of the stratification, f is the Coriolis parameter, and h is the ocean depth). The second and third are, respectively, "fast" and "slow" westward regimes little affected by topography and associated with the first and second bottom-pressure-compensated normal modes studied in previous work by Tailleux and McWilliams. Idealized examples show that actual rays can often be reproduced with reasonable accuracy by replacing the actual dispersion relation by its QND approximation. The topographic regime provides an upper bound ( in general a large overestimate) of the maximum latitudinal excursions of actual rays. The method presented in this paper is interesting for enabling an optimal classification of purely azimuthally dispersive wave systems into simpler idealized QND wave regimes, which helps to rationalize previous empirical findings that the ray paths of long Rossby waves in the presence of mean flow and topography often seem to be independent of the wavenumber orientation. Two important side results are to establish that the baroclinic string function regime of Tyler and K se is only valid over a tiny range of the topographic parameter and that long baroclinic Rossby waves propagating over topography do not obey any two-dimensional potential vorticity conservation principle. Given the importance of the latter principle in geophysical fluid dynamics, the lack of it in this case makes the concept of the QND regimes all the more important, for they are probably the only alternative to provide a simple and economical description of general purely azimuthally dispersive wave systems.

Quasi-biennial oscillation and tracer distributions in a coupled chemistry-climate model

[ 1] We have used a fully coupled chemistry-climate model (CCM), which generates its own wind and temperature quasi-biennial oscillation (QBO), to study the effect of coupling on the QBO and to examine the QBO signals in stratospheric trace gases, particularly ozone. Radiative coupling of the interactive chemistry to the underlying general circulation model tends to prolong the QBO period and to increase the QBO amplitude in the equatorial zonal wind in the lower and middle stratosphere. The model ozone QBO agrees well with Stratospheric Aerosol and Gas Experiment II and Total Ozone Mapping Spectrometer satellite observations in terms of vertical and latitudinal structure. The model captures the ozone QBO phase change near 28 km over the equator and the column phase change near +/- 15 degrees latitude. Diagnosis of the model chemical terms shows that variations in NOx are the main chemical driver of the O-3 QBO around 35 km, i.e., above the O-3 phase change.

Testing the limits of quasi-geostrophic theory: application to observed laboratory flows outside the quasi-geostrophic regime

We compare laboratory observations of equilibrated baroclinic waves in the rotating two-layer annulus, with numerical simulations from a quasi-geostrophic model. The laboratory experiments lie well outside the quasi-geostrophic regime: the Rossby number reaches unity; the depth-to-width aspect ratio is large; and the fluid contains ageostrophic inertia–gravity waves. Despite being formally inapplicable, the quasi-geostrophic model captures the laboratory flows reasonably well. The model displays several systematic biases, which are consequences of its treatment of boundary layers and neglect of interfacial surface tension and which may be explained without invoking the dynamical effects of the moderate Rossby number, large aspect ratio or inertia–gravity waves. We conclude that quasi-geostrophic theory appears to continue to apply well outside its formal bounds.

Perturbed Rankine vortices in surface quasi-geostrophic dynamics

An analytical dispersion relation is derived for linear perturbations to a Rankine vortex governed by surface quasi-geostrophic dynamics. Such a Rankine vortex is a circular region of uniform anomalous surface temperature evolving under quasi-geostrophic dynamics with uniform interior potential vorticity. The dispersion relation is analysed in detail and compared to the more familiar dispersion relation for a perturbed Rankine vortex governed by the Euler equations. The results are successfully verified against numerical simulations of the full equations. The dispersion relation is relevant to problems including wave propagation on surface temperature fronts and the stability of vortices in quasi-geostrophic turbulence.

Force constants and dipole‐moment derivatives of molecules from perturbed Hartree–Fock calculations

General expressions for the force constants and dipole‐moment derivatives of molecules are derived, and the problems arising in their practical application are reviewed. Great emphasis is placed on the use of the Hartree–Fock function as an approximate wavefunction, and a number of its properties are discussed and re‐emphasised. The main content of this paper is the development of a perturbed Hartree–Fock theory that makes possible the direct calculation of force constants and dipole‐moment derivatives from SCF–MO wavefunctions. Essentially the theory yields ∂ϕi / ∂RJα, the derivative of an MO with respect to a nuclear coordinate.

The calculation of force constants and normal coordinates IV: XH4 and XH3 molecules

Normal coordinate calculations of XH4 and XH3 molecules are reviewed and discussed. It is shown that for most of these molecules the true values of the force constants in the most General Harmonic Force Field can be uniquely determined only by making use of vibration-rotation interaction constants. It is emphasized that without these extra data the GFF is not determined. The results are compared with various model force fields for these molecules.

Analytical potentials for triatomic molecules IX. The prediction of anharmonic force constants from potential energy surfaces based on harmonic force fields and dissociation energies for SO2 and O3

Analytical potential energy functions which are valid at all dissociation limits have been derived for the ground states of SO2 and O3. The procedure involves minimizing the errors between the observed vibrational spectra and spectra calculated by a variational procedure. Good agreement is obtained between the observed and calculated spectra for both molecules. Comparisons are made between anharmonic force fields, previously determined from the spectral data, and the force fields obtained by differentiating the derived analytical functions at the equilibrium configurations.

Analytical potentials for triatomic molecules from spectroscopic data V. Application to HOX (X=F, Cl, Br, I)

Analytical potential energy functions are reported for HOX (X=F, Cl, Br, I). The surface for HOF predicts two metastable minima as well as the equilibrium configuration. These correspond to HFO (bent) and OHF (linear). Ab initio calculations performed for the HOF surface confirm these predictions. Comparisons are drawn between the two sets of results, and a vibrational analysis is undertaken for the hydrogen bonded OHF species. For HOCl, one further minimum is predicted, corresponding to HClO (bent), the parameters for which compare favourably with those reported from ab initio studies. In contrast, only the equilibrium configurations are predicted to be stable for HOBr and HOI.

Selection rules for rovibronic transitions in symmetric top molecules

A simple diagrammatic rule is presented for determining the rotational selection rules governing transitions between any pair of vibronic states in electric dipole spectra of symmetric top molecules. The rule is useful in cases where degenerate vibronic levels with first-order Coriolis splittings occur, because it gives immediately the selection rule for the (+l) and (-l) components in any degenerate state. The rule is also helpful in determining the symmetry species and the effective zeta constants in overtone and combination levels involving degenerate vibrations. Particular attention is devoted to the conventions concerning the signs of zeta constants.

Force constants and dipole moment derivatives of molecules from perturbed Hartree-Fock calculations II. Applications to limited basis set SCF-MO wavefunctions

The perturbed Hartree–Fock theory developed in the preceding paper is applied to LiH, BH, and HF, using limited basis‐set SCF–MO wavefunctions derived by previous workers. The calculated values for the force constant ke and the dipole‐moment derivative μ(1) are (experimental values in parentheses): LiH, ke  =  1.618(1.026)mdyn/Å,μ(1)  =  −18.77(−2.0±0.3)D/ÅBH,ke  =  5.199(3.032)mdyn/Å,μ(1)  =  −1.03(−)D/Å;HF,ke  =  12.90(9.651)mdyn/Å,μ(1)  =  −2.15(+1.50)D/Å. The values of the force on the proton were calculated exactly and according to the Hellmann–Feynman theorem in each case, and the discrepancies show that none of the wavefunctions used are close to the Hartree–Fock limit, so that the large errors in ke and μ(1) are not surprising. However no difficulties arose in the perturbed Hartree–Fock calculation, so that the application of the theory to more accurate wavefunctions appears quite feasible.

Raman selection rules for vibration-rotation transitions in symmetric top molecules

Symmetry restrictions on Raman selection rules can be obtained, quite generally, by considering a Raman allowed transition as the result of two successive dipole allowed transitions, and imposing the usual symmetry restrictions on the dipole transitions. This leads to the same results as the more familiar polarizability theory, but the vibration-rotation selection rules are easier to obtain by this argument. The selection rules for symmetric top molecules involving the (+l) and (-l) components of a degenerate vibrational level with first-order Coriolis splitting are derived in this paper. It is shown that these selection rules depend on the order of the highest-fold symmetry axis Cn, being different for molecules with n=3, n=4, or n ≧ 5; moreover the selection rules are different again for molecules belonging to the point groups Dnd with n even, and Sm with 1/2m even, for which the highest-fold symmetry axes Cn and Sm are related by m=2n. Finally it is shown that an apparent anomaly between the observed Raman and infra-red vibration-rotation spectra of the allene molecule is resolved when the correct selection rules are used, and a value for the A rotational constant of allene is derived without making use of the zeta sum rule.