Modulation of amyloid-β aggregation by metal complexes with a dual binding mode and their delivery across the blood–brain barrier using focused ultrasound

One of the key hallmarks of Alzheimer''s disease is the aggregation of the amyloid-β peptide to form fibrils. Consequently, there has been great interest in studying molecules that can disrupt amyloid-β aggregation. While a handful of molecules have been shown to inhibit amyloid-β aggregation in vitro, there remains a lack of in vivo data reported due to their inability to cross the blood–brain barrier. Here, we investigate a series of new metal complexes for their ability to inhibit amyloid-β aggregation in vitro. We demonstrate that octahedral cobalt complexes with polyaromatic ligands have high inhibitory activity thanks to their dual binding mode involving π–π stacking and metal coordination to amyloid-β (confirmed via a range of spectroscopic and biophysical techniques). In addition to their high activity, these complexes are not cytotoxic to human neuroblastoma cells. Finally, we report for the first time that these metal complexes can be safely delivered across the blood–brain barrier to specific locations in the brains of mice using focused ultrasound.

We report a series of non-toxic cobalt(iii) complexes which inhibit Aβ peptide aggregation in vitro; these complexes can be safely delivered across the blood–brain barrier in mice using focused ultrasound.     

Swelling of dextran gel and osmotic pressure of soluble dextran in the presence of salts

The swelling of dextran gels (Sephadex) in salt solutions with a water activity of 0.937, compared with the swelling in pure water, exhibited anion specificity as evidenced by an increased swelling ratio in the following order: Na₂SO₄ < H₂O < NaCl < NaSCN. The swelling ratio showed a good linear correlation with the osmotic pressure of dextran (500 kD) in these solutions. The salt‐concentration difference (imbalance) between the polymer‐solution side of the membrane and the polymer‐free permeate side during the osmotic‐pressure measurements positively correlated with the effect of the salt on the polymer osmotic pressure. These phenomena conform to Hofmeister‐type (or lyotropic) behavior. The diminishing augmentation of dextran osmotic pressure and the change in the salt‐concentration imbalance with rising NaSCN concentration imply a positive preferential interaction and adsorption of the salt onto the polymer. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 2740–2750, 2001     

Design of an active suspension to suppress the horizontal vibrations of a spray boom

Spray-boom vibrations are one of the main causes of a non-homogeneous distribution of agro-chemicals. Yawing and jolting motions of the boom are most critical. A horizontal active suspension, reducing yawing and jolting is designed. The use of special and consequently expensive equipment hampers the breakthrough of active suspensions. Therefore the proposed active suspension is built from standard hydraulic equipment, suited for mobile applications. Coulomb friction and asymmetric behaviour introduces considerable non-linearities, complicating the derivation of a linear model and controller design. It is explained how to identify a model, approximating in the best-possible way the general linear behaviour of the system. By the H^∞ methodology and an iterative procedure, introduced in this paper, non-linearities are taken into account in the controller design without increasing the controller dimensions. The resulting controller is stable and shows good performance.     

Means of unitaries, conjugations, and the Friedrichs operator

If C is a conjugation (an isometric, conjugate-linear involution) on a separable complex Hilbert space H, then T∈B(H) is called C-symmetric if T=CT^∗C. In this note we prove that each C-symmetric contraction T is the mean of two C-symmetric unitary operators. We discuss several corollaries and an application to the Friedrichs operator of a planar domain.     

Ueber eine allgemeinere Theorie der Adsorption von Lösungen

Ohne Zusammenfassung     

The Physical Origin of Interfacial Coupling in Two-Phase Flow through Porous Media

Recently developed transport equations for two-phase flow through porous media usually have a second term that has been included to account properly for interfacial coupling between the two flowing phases. The source and magnitude of such coupling is not well understood. In this study, a partition concept has been introduced into Kalaydjian's transport equations to construct modified transport equations that enable a better understanding of the role of interfacial coupling in two-phase flow through natural porous media. Using these equations, it is demonstrated that, in natural porous media, the physical origin of interfacial coupling is the capillarity of the porous medium, and not interfacial momentum transfer, as is usually assumed. The new equations are also used to show that, under conditions of steady-state flow, the magnitude of mobilities measured in a countercurrent flow experiment is the same as that measured in a cocurrent flow experiment, contrary to what has been reported previously. Moreover, the new equations are used to explicate the mechanism by which a saturation front steepens in an unstabilized displacement, and to show that the rate at which a wetting fluid is imbibed into a porous medium is controlled by the capillary coupling parameter, . Finally, it is argued that the capillary coupling parameter, , is dependent, at least in part, on porosity. Because a clear understanding of the role played by interfacial coupling is important to an improved understanding of two-phase flow through porous media, the new transport equations should prove to be effective tools for the study of such flow.     

Simultaneous spreading and evaporation: Recent developments

The recent progress in theoretical and experimental studies of simultaneous spreading and evaporation of liquid droplets on solid substrates is discussed for pure liquids including nanodroplets, nanosuspensions of inorganic particles (nanofluids) and surfactant solutions. Evaporation of both complete wetting and partial wetting liquids into a nonsaturated vapour atmosphere are considered. However, the main attention is paid to the case of partial wetting when the hysteresis of static contact angle takes place. In the case of complete wetting the spreading/evaporation process proceeds in two stages. A theory was suggested for this case and a good agreement with available experimental data was achieved. In the case of partial wetting the spreading/evaporation of a sessile droplet of pure liquid goes through four subsequent stages: (i) the initial stage, spreading, is relatively short (1–2 min) and therefore evaporation can be neglected during this stage; during the initial stage the contact angle reaches the value of advancing contact angle and the radius of the droplet base reaches its maximum value, (ii) the first stage of evaporation is characterised by the constant value of the radius of the droplet base; the value of the contact angle during the first stage decreases from static advancing to static receding contact angle; (iii) during the second stage of evaporation the contact angle remains constant and equal to its receding value, while the radius of the droplet base decreases; and (iv) at the third stage of evaporation both the contact angle and the radius of the droplet base decrease until the drop completely disappears. It has been shown theoretically and confirmed experimentally that during the first and second stages of evaporation the volume of droplet to power 2/3 decreases linearly with time. The universal dependence of the contact angle during the first stage and of the radius of the droplet base during the second stage on the reduced time has been derived theoretically and confirmed experimentally. The theory developed for pure liquids is applicable also to nanofluids, where a good agreement with the available experimental data has been found. However, in the case of evaporation of surfactant solutions the process deviates from the theoretical predictions for pure liquids at concentration below critical wetting concentration and is in agreement with the theoretical predictions at concentrations above it.     

Logical Kronecker delta deconstruction of the absolute value function and the treatment of absolute deviations

A logical Kronecker delta reformulation of the absolute value function and the related discrete problem of the optimal absolute deviation are studied as the basic step towards applications of first order norms in theoretical chemistry. Absolute value function derivatives appear in the present context related to unit step function, Dirac delta function and its derivatives. The absolute value of the difference of two Minkowski normalized Gaussian functions is analyzed as an example. The proposed logical Kronecker delta deconstruction manner to express the absolute value function is also applied to the absolute deviation from the median of a set of numerical values, which looks to be just the optimal first order norm.