Pre-formulation of an oral cyclosporine free of surfactant

The purpose of this study was to develop a new oral cyclosporine A (CsA) formulation free of surfactant cremophor using cyclodextrin terpolymers (P-αβ-CD, P-βγ-CD and P-αγ-CD) as excipients in attempt to enhance its stability, dissolution rate and eliminate surfactant side effects. Two spray-dried dispersions (SDDs) containing poorly water-soluble CsA were prepared with either P-αβ-CD, P-βγ-CD or P-αγ-CD using water ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) and ethanol (F _EOH) via spray-drying technique and characterized by scanning electron microscopy, powder X-ray diffraction, particle size distribution, circular dichroism (CD) and nuclear magnetic resonance along with the dissolution study which was compared to Neoral^® and Sandimmune^®. The results showed an interaction between CsA and P-αβ-CD, P-βγ-CD and P-αγ-CD without secondary structure change of CsA. The order of the CsA release from the terpolymers was ranked as follows: P-αγ-CD/CsA ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) = Neoral^® > P-βγ-CD/CsA ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) > P-αβ-CD/CsA ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) > P-αγ-CD/CsA (F _EOH) > Sandimmune^® > P-αβ-CD/CsA (F _EOH) > P-βγ-CD/CsA (F _EOH). The results of ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) could be explained by hydrophilisation and absence of crystallinity of CsA while maintaining part of its crystallinity in the case of formulations (F _EOH). In summary, developed SDD formulations P-αγ-CD/CsA ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) revealed same dissolution profile as Neoral^® and better than Sandimmune^®. These systems seem to be stable to carry cyclosporine and release it, while preserving structure and thus, potentially, also maintaining cyclosporine activity.     

On weakly τ-quasinormal subgroups of finite groups

Let G be a finite group and H a subgroup of G. We say that: (1) H is τ-quasinormal in G if H permutes with all Sylow subgroups Q of G such that (|Q|, |H|) = 1 and (|H|, |Q ^G |) ≠ 1; (2) H is weakly τ-quasinormal in G if G has a subnormal subgroup T such that HT = G and T ∩ H ≦ H _τG , where H _τG is the subgroup generated by all those subgroups of H which are τ-quasinormal in G. Our main result here is the following. Let ℱ be a saturated formation containing all supersoluble groups and let X ≦ E be normal subgroups of a group G such that G/E ∈ ℱ. Suppose that every non-cyclic Sylow subgroup P of X has a subgroup D such that 1 < |D| < |P| and every subgroup H of P with order |H| = |D| and every cyclic subgroup of P with order 4 (if |D| = 2 and P is non-Abelian) not having a supersoluble supplement in G is weakly τ-quasinormal in G. If X is either E or F* (E), then G ∈ ℱ.     

Local embeddings of some families of subgroups of finite groups

In this paper we study the influence of the partial cover and avoidance property on the subgroups of some relevant families of subgroups in a finite group.     

A continuation principle for Fredholm maps II: application to homoclinic solutions

When studying the behavior of autonomous ordinary differential equations under time-dependent perturbations vanishing for $t\to \pm \infty$, their equilibria generically persist locally as homoclinic solutions. Using an abstract and flexible continuation theorem, we find even global branches of such homoclinic solutions for parametrized nonautonomous ordinary differential equations. Our approach is based on degree-theoretical arguments. In particular, Landesman–Lazer conditions are proposed to obtain the existence of homoclinic solutions by means of a nonzero degree.     

Solution of the linear and nonlinear advection–diffusion problems on a sphere

Various linear advection–diffusion problems and nonlinear diffusion problems on a sphere are considered and solved using the direct, implicit and unconditionally stable finite-volume method of second-order approximation in space and time. In the absence of external forcing and dissipation, the method preserves the total mass of the substance and the norm of the solution. The component wise operator splitting allows us to develop the direct (noniterative) and fast numerical algorithm. The split problems in the longitudinal direction are solved using the Sherman-Morrison formula and Thomas algorithm. The direct solution of the split problems in the latitudinal direction requires the use of the bordering method for a block matrix, and the preliminary determination of the solution at the poles. The resulting systems with tridiagonal matrices are solved by the Thomas algorithm. The numerical experiments demonstrate that the method correctly describes the local advection–diffusion processes on the sphere, in particular, through the poles, and accurately simulate blow-up regimes (unlimited growing solutions) of nonlinear combustion, the propagation of nonlinear temperature and spiral waves, and solutions to Gray-Scott reaction–diffusion model.     

On the existence and uniqueness of solution to problems of fluid dynamics on a sphere

Orthogonal projectors and fractional derivatives on a two-dimensional unit sphere are introduced. Hilbert and Banach spaces of smooth functions on the sphere and some embedding assertions are given. The unique solvability of a nonstationary problem of vortex dynamics of viscous incompressible fluid on a rotating sphere is shown. The existence of a weak solution to stationary problem is proved too, and a condition guaranteeing the uniqueness of solution is also given.     

Emission of partial dislocations by grain boundaries in nanocrystalline metals

A theoretical model is proposed to describe the emission of partial dislocations by grain boundaries in nanocrystalline materials during plastic deformation. Partial dislocations are assumed to be emitted during the motion of grain-boundary disclinations, which are carriers of rotational plastic deformation. The ranges of the parameters of a defect structure in which the emission of partial dislocations by grain boundaries in nanocrystalline metals are energetically favorable are calculated. It is shown that, as the size of a grain decreases, the emission of partial dislocations by its boundary becomes more favorable as compared to the emission of perfect lattice dislocations.     

Crack-stimulated generation of deformation twins in nanocrystalline metals and ceramics

A theoretical model is proposed that describes the generation of deformation twins near brittle cracks of mixed I and II modes in nanocrystalline metals and ceramics. In the framework of the model, a deformation twin nucleates through stress-driven emission of twinning dislocations from a grain boundary distant from the crack tip. The emission is driven by both the external stress concentrated by the pre-existent crack and the stress field of a neighbouring extrinsic grain boundary dislocation. The ranges of the key parameters, the external shear stress, τ, and the crack length, L, are calculated within which the deformation-twin formation near pre-existent cracks is energetically favourable in a typical nanocrystalline metal (Al) and ceramic (3C-SiC). The results of the proposed model account for experimental data on observation of deformation twins in nanocrystalline materials reported in the literature. The deformation-twin formation is treated as a toughening mechanism effectively operating in nanocrystalline metals and ceramics.     

Subcellular localization of the antidepressant-sensitive norepinephrine transporter

Background  

Reuptake of synaptic norepinephrine (NE) via the antidepressant-sensitive NE transporter (NET) supports efficient noradrenergic signaling and presynaptic NE homeostasis. Limited, and somewhat contradictory, information currently describes the axonal transport and localization of NET in neurons.