An expedient synthesis of the fibril binding compound FSB via sequential Pd-catalyzed coupling reactions

The styryl benzene derivative (E, E)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (FSB), well-known for its binding to beta-amyloid peptide fibrils, was synthesized in an efficient manner exploiting two sequential palladium(0)-catalyzed coupling reactions in a 34% overall yield. This is a substantial improvement to the previously reported synthesis of FSB in 1.1%.     

Mean‐Field Evolution of Fermionic Mixed States

In this paper we study the dynamics of fermionic mixed states in the mean‐field regime. We consider initial states that are close to quasi‐free states and prove that, under suitable assumptions on the initial data and on the many‐body interaction, the quantum evolution of such initial data is well approximated by a suitable quasi‐free state. In particular, we prove that the evolution of the reduced one‐particle density matrix converges, as the number of particles goes to infinity, to the solution of the time‐dependent Hartree‐Fock equation. Our result holds for all times and gives effective estimates on the rate of convergence of the many‐body dynamics towards the Hartree‐Fock evolution.© 2015 Wiley Periodicals, Inc.     

Elucidation of control mechanisms discovered during adaptive manipulation of [Ru(dpb)3](PF6)2 emission in the solution phase

To design methodologies that will allow researchers to directly correlate the results of adaptive control experiments with physiochemical control pathways in arbitrary complex molecular systems it is imperative that prototype systems are developed and that exigent control pathways are understood. We have been interested in the results of adaptive control experiments in our laboratory involving the maximization of a ratio of two experimental observables: (1) the thermalized emission from the solution-phase coordination complex [Ru(dpb)3](PF6)2 and (2) the second harmonic signal (a purely intensity-dependent phenomenon) of the shaped laser fields. Using a rational pulse shaping strategy, we have made a measurement of the ratio spectrum (in essence the two-photon absorption cross section) for the molecule [Ru(dpb)3](PF6)2 in a room temperature solution of acetonitrile. This spectrum is highly varied across the accessible two-photon power spectrum of our broad-band laser pulses and demonstrates the existence of a control pathway wherein a shaped laser field can manipulate excited-state population (with respect to SHG) by conforming to the second-order spectral response of the molecule in solution. We show that our adaptive control algorithm is capable of taking advantage of these control pathways using simulated adaptive control experiments. Finally, we measure second-harmonic spectra of shaped laser fields discovered during an adaptive control experiment and show that these agree with simulation. These results suggest that our adaptive control experiment can be understood in the context of the elucidated spectral control pathway.     

Tumor selectivity at short times following systemic administration of a liposomal temoporfin formulation in a murine tumor model

Meso-tetra(hydroxyphenyl)chlorin (mTHPC) (INN: Temoporfin) is one of the most potent photodynamically active substances in clinical use. Treatment protocols for Temoporfin-mediated photodynamic therapy often rely on drug-light intervals of several days in order for the photosensitizer to accumulate within the target tissue, though tumor selectivity is limited. Here, the mTHPC localization was studied at 2-8 h following systemic administration of a liposomal Temoporfin formulation (0.15 mg kg(-1) b.w.) in HT29 human colon adenocarcinoma in NMRI nu/nu mice. Photosensitizer distribution within tumor and internal organs was investigated by means of high performance liquid chromatography following chemical extraction, as well as in situ fluorescence imaging and point-monitoring fluorescence spectroscopy. For tumor tissue, the Temoporfin concentrations at 4 h (0.16+/-0.024 ng mg(-1)) and 8 h (0.18+/-0.064 ng mg(-1)) were significantly higher than at 2 h (0.08+/-0.026 ng mg(-1)). The average tumor-to-muscle and the tumor-to-skin selectivity were 6.6 and 2, respectively, and did not vary significantly with time after photosensitizer injection. In plasma, the Temoporfin concentration was low (0.07+/-0.07 ng mg(-1)) and showed no significant variation with time. Our results indicate a rapid biodistribution and clearance from the bloodstream. Within the same type of organ, data from both fluorescence methods generally exhibited a significant correlation with the extraction results.     

Tapered laser cooling of stored coasting ion beams

We propose a scheme for tapered laser cooling of coasting ion beams in storage rings. Tapered cooling has recently been shown to be crucial for attaining crystalline ion beams. The scheme proposed here, based on a relative displacement of a co- and a counterpropagating Gaussian laser beam, gives a radial variation in the equilibrium velocities to which particles are cooled. The variation is approximately linear in a relatively large range transverse to the laser beams. Expressions for the spatially dependent equilibrium velocities and the range of the tapered cooling forces are derived. We discuss the dependence on laser beam parameters as well as the limitations of this cooling scheme.     

Optimal design of vibrating rectangular plates

The thickness function of a simply supported rectangular plate is determined such that the fundamental natural frequency of transverse vibrations attains an optimum value. The volume of the solid plate, its size, and data pertaining to its material properties, are assumed to be given.The problem consists of determining the deflection function corresponding to the optimal plate thickness function from a non-linear, fourth order partial differential eigenvalue problem, derived by variational analysis.Second and higher order normal derivatives of the deflection function are singular along the boundary of the domain. This behaviour is investigated analytically, and taken into account in a finite difference formulation of the problem, which is solved numerically by successive iterations.     

Dissipation-Dependent Thermal Escape from a Potential Well

Langevin simulations are conducted to investigate the Josephson escape statistics over a large set of parameter values for damping and temperature. The results are compared to both Kramers and Büttiker–Harris–Landauer (BHL) models, and good agreement is found with the Kramers model for high to moderate damping, while the BHL model provides further good agreement down to lower damping values. However, for extremely low damping, even the BHL model fails to reproduce the progression of the escape statistics. In order to explain this discrepancy, we develop a new model which shows that the bias sweep effectively cools the system below the thermodynamic value as the potential well broadens due to the increasing bias. A simple expression for the temperature is derived, and the model is validated against direct Langevin simulations for extremely low damping values.     

On the Mechanism of Polyamide Degradation in Chlorinated Water

Experiments were performed in an attempt to identify the reactive intermediate(s) involved in the degradation of a polyamide, Nylon 66, in chlorinated water. According to previous studies, N‐chlorination is certainly one reaction that ultimately contributes to polyamide degradation. In this case, the intermediates involved could either be Cl₂ or HClO. Available information also indicates that, for many polymers, singlet molecular oxygen (a¹Δ_g), chemically generated from HClO, could likewise be involved as an intermediate in a degradation reaction. Thus, tests were undertaken to specifically address this latter issue with respect to polyamide degradation. The degradation of Nylon 66 was monitored under a variety of conditions by FT‐IR spectroscopy. The rate of degradation was pH‐dependent, and degradation was most pronounced at pH<5. Characteristic tests for the intermediacy of singlet oxygen, however, were negative. Rather, the data strongly pointed to Cl₂ as the key intermediate in the degradation. The presence of compounds capable of being oxidized by Cl₂ arrested the degradation reaction. These results should be pertinent in an attempt to stabilize polymers exposed, e.g., to water that has been chlorinated to kill bacteria (i.e., drinking water).