Probing small molecule binding to amyloid fibrils

Much effort has focussed in recent years on probing the interactions of small molecules with amyloid fibrils and other protein aggregates. Understanding and control of such interactions are important for the development of diagnostic and therapeutic strategies in situations where protein aggregation is associated with disease. In this perspective article we give an overview over the toolbox of biophysical methods for the study of such amyloid-small molecule interactions. We discuss in detail two recently developed techniques within this framework: linear dichroism, a promising extension of the more traditional spectroscopic techniques, and biosensing methods, where surface-bound amyloid fibrils are exposed to solutions of small molecules. Both techniques rely on the measurement of physical properties that are very directly linked to the binding of small molecules to amyloid aggregates and therefore provide an attractive route to probe these important interactions.     

Solutions to and Validation of Matrix-Diffusion Models

A model transport system is considered in which a pulse of tracer molecules is advected along a flow channel with porous walls. The advected tracer thus undergoes diffusion, matrix-diffusion, inside the walls, which affects the breakthrough curve of the tracer. Analytical solutions in the form of series expansions are derived for a number of situations which include a finite depth of the porous matrix, varying aperture of the flow channel, and longitudinal diffusion and Taylor dispersion of the tracer in the flow channel. Novel expansions for the Laplace transforms of the concentration in the channel facilitated closed-form expressions for the solutions. A rigorous result is also derived for the asymptotic form of the breakthrough curve for a finite depth of the porous matrix, which is very different from that for an infinite matrix. A specific experimental system was created for validation of matrix-diffusion modeling for a matrix of finite depth. A previously reported fracture-column experiment was also modeled. In both cases model solutions gave excellent fits to the measured breakthrough curves with very consistent values for the diffusion coefficients used as the fitting parameters. The matrix-diffusion modeling performed could thereby be validated.     

Quantum Diffusion and Delocalization for Band Matrices with General Distribution

We consider Hermitian and symmetric random band matrices H in d \geqslant 1{d \geqslant 1} dimensions. The matrix elements H _xy , indexed by x,y ? L ì \mathbbZ^d{x,y \in \Lambda \subset \mathbb{Z}^d}, are independent and their variances satisfy s_xy²:=\mathbbE |H_xy|² = W^-d f((x - y)/W){\sigma_{xy}^2:=\mathbb{E} |{H_{xy}}|^2 = W^{-d} f((x - y)/W)} for some probability density f. We assume that the law of each matrix element H _xy is symmetric and exhibits subexponential decay. We prove that the time evolution of a quantum particle subject to the Hamiltonian H is diffusive on time scales t << W^d/3{t\ll W^{d/3}} . We also show that the localization length of the eigenvectors of H is larger than a factor W^d/6{W^{d/6}} times the band width W. All results are uniform in the size |Λ| of the matrix. This extends our recent result (Erdős and Knowles in Commun. Math. Phys., 2011) to general band matrices. As another consequence of our proof we show that, for a larger class of random matrices satisfying ?_xs_xy²=1{\sum_x\sigma_{xy}^2=1} for all y, the largest eigenvalue of H is bounded with high probability by 2 + M^{-2/3 + e}{2 + M^{-2/3 + \varepsilon}} for any ${\varepsilon > 0}${\varepsilon > 0}, where M : = 1 / (max_x,ys_xy²){M := 1 / (\max_{x,y}\sigma_{xy}^2)} .     

Investigation of muonic hydrogen isotopes scattering from H2 molecule

Hyperfine Interactions - Knowledge of the cross sections for scattering of µp, µd and µt on molecules of hydrogen isotopes is necessary not only for checking the algorithmic solution...     

Velocity distributions in glottal models

Velocity distributions within three models of the human larynx, namely, a rigid plexiglas model, an excised canine larynx, and a computational model are investigated with experimental and theoretical analyses. A plexiglas wind tunnel with interchangeable glottal constrictions was used as a two-dimensional steady-flow model to measure velocity and pressure for various glottal shapes. A canine excised larynx was used as a prototype pulsatile flow model to study pressure and velocity variations during phonation. Results of the plexiglas modelling indicated a parabolic laminar velocity profile upstream of the glottal constriction and turbulent and asymmetric velocity profiles downstream of the glottal constriction. The time-averaged velocities of the excised larynx had similarities with the plexiglas model results, and instabilities and asymmetries were also demonstrated by the computational method.     

A frequency doubler for 200 GHz with a planar Schottky varactor

A frequency doubler for 200 GHz utilising a planar surface channel Schottky varactor was designed, constructed and tested. The doubler employes novel split-waveguide mount design with two sliding backshorts at both input and output waveguides. The theoretical maximum efficiency of the doubler is 44.0 % with input power level of 32 mW and the maximum output power is 16.5 mW with input power level of 50 mW. The measured maximum efficiency of the doubler was 7.1 % and the maximum output power was 2.6 mW     

OBITUARY

E dna R oe died on 31 July, 1971, in London after a long illness borne cheerfully and with great courage. This was typical of Edna, who had often given courage and hope to others in similar situations.
Edna Margaret Frances Roe was born and educated in London and worked there for most of her life. Soon after graduating she joined the staff of the Research Institute of the Royal Cancer Hospital to work with W. V. Mayneord on the absorption spectra of carcinogenic hydrocarbons. This work included a study of the fluorescence of these molecules and this encounter with the excited state led to a sustained interest in the photochemistry of biologically active molecules, particularly in the fields of photodynamic action and the UV degradation of nucleic acids.     

On the spatial decay of solutions of the heat equation

Zusammenfassung Es werden Energieungleichungen aufgestellt, welche die exponentielle räumliche Abnahme der Lösungen der Wärmegleichung ausdrücken.

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This research is based on work supported in part by the United States Office of Naval Research under Contract Nonr 220(56). Reproduction in whole or in part is permitted for any purpose of the United States Government.