One of the great challenges in pharmacokinetics is to find a means to optimize the transport across cell barriers. In this work, permeation across a cell monolayer, such as the tight endothelia in the blood-brain barrier, was modeled using a homologous series of amphipatic molecules, 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled alkyl chain amphiphiles (NBD-Cn, n = 2 to 16), to obtain rules that relate permeant structure to permeability. The amphiphile enters the system from the serum, equilibrated with serum albumin and lipoproteins, and its sequestration by serum components, interaction with the endothelium, and accumulation in the tissue is followed over time. The dependence of the permeability coefficient on the number of carbons of the amphiphile's alkyl chain has a parabolic-like shape. After a threshold value, an increase in the hydrophobicity of the amphiphile, along the homologous series, results in a decrease in the characteristic rate of permeation to the tissue. A sensitivity analysis was performed, and the rate limiting steps for permeation of each amphiphile were identified. Sequestration in the serum and rate of interaction with the endothelium, particularly the rate of desorption, were found to be the determinant processes for some amphiphiles, while for others translocation was the rate limiting step. Additionally, for some amphiphiles a single rate limiting step could not be identified, with several steps contributing significantly to the overall permeation. Finally, we derived analytical equations that adequately describe the rate of amphiphile accumulation in the tissue for the cases where permeation is controlled by a single rate limiting step.

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We have determined the structure of (BP)0.08(BPI)0.92 both in the ferrodistortive (at ≈︂294 K) and in the ferroelectric (at ≈︂146 K) phases, by single crystal X‐ray diffraction measurements. A detailed comparison between the structures revealed small but significant structural distortions, consisting almost exclusively of rotations which evidence the order–disorder nature of protons in the bonds linking neighbouring molecules in the chains and confirm the increase of the hybridization of the orbitals of the O–H valence electrons in these bonds upon cooling. These observations suggest that the proton ordering may be, if not the only contribution to the macroscopic polarization, at least the mechanism triggering the para–ferroelectric phase transition in (BP)0.08(BPI)0.92.

Abstract-Transcranial magnetic stimulation (TMS) was proposed in 1985. Nevertheless, its wider use in the treatment of several neurologic diseases has been hindered by its inability to stimulate deep-brain regions. This is mainly due to the physical limiting effect arising from the presence of surface discontinuities, particularly between the scalp and air. Here, we present the optimization of a system of large multiple coils for whole-brain and half-hemisphere deep TMS, termed orthogonal configuration. COMSOL ® -based simulations show that the system is capable of reaching the very center of a spherical brain phantom with 58% induction relative to surface maximum. Such penetration capability surpasses to the best of our knowledge that of existing state of the art TMS systems. This induction capability strongly relies on the immersion of the stimulating coils and part of the head of the patient in a conducting liquid (e.g. simple saline solution). We show the impact of the presence of this surrounding conducting liquid by comparing the performance of our system with and without such liquid. In addition, we also compare the performance of the proposed coil with that of a circular coil, a figure-eight coil, and the H-coil. Finally, in addition to its whole-brain stimulation capability (e.g. potentially useful for prophylaxis of epileptic patients) the system is also able to stimulate mainly one brain hemisphere, which may be useful in stroke rehabilitation, among other applications.