(2′‐O‐Methyl‐RNA)‐3′‐PNA Chimeras: A New Class of Mixed Backbone Oligonucleotide Analogues with High Binding Affinity to RNA

The automated on‐line synthesis of DNA‐3′‐PNA chimeras 1 – 4 and (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras 5 – 8 is described, in which the 3′‐terminal part of the oligonucleotide is linked to the N‐terminal part of the PNA via N‐(ω‐hydroxyalkyl)‐N‐[(thymin‐1‐yl)acetyl]glycine units (alkyl=Et, Ph, Bu, and pentyl). By means of UV thermal denaturation, the binding affinities of all chimeras were directly compared by determining their T_m values in the duplex with complementary DNA and RNA. All investigated DNA‐3′‐PNA chimeras and (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras form more‐stable duplexes with complementary DNA and RNA than the corresponding unmodified DNA. Interestingly, a N‐(3‐hydroxypropyl)glycine linker resulted in the highest binding affinity for DNA‐3′‐PNA chimeras, whereas the (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras showed optimal binding with the homologous N‐(4‐hydroxybutyl)glycine linker. The duplexes of (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras and RNA were significantly more stable than those containing the corresponding DNA‐3′‐PNA chimeras. Surprisingly, we found that the charged (2′‐O‐methyl‐RNA)‐3′‐PNA chimera with a N‐(4‐hydroxybutyl)glycine‐based unit at the junction to the PNA part shows the same binding affinity to RNA as uncharged PNA. Potential applications of (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras include their use as antisense agents acting by a RNase‐independent mechanism of action, a prerequisite for antisense‐oligonucleotide‐mediated correction of aberrant splicing of pre‐mRNA.     

Antisense-Oligonucleotide – ein universelles Therapieprinzip

In recent years, a nova1 class of pharmaceuticals has been developed which bind in a predictable way to certain nucleic acid target sequences aiming at selective inhibition of expression of disease-causing genes. The chemical structure of these so-called antisense oligonucleotide compounds must be altered relative to their natural models to render them stable under in vivo conditions and to allow their penetration to the site of action inside cells. In this article, the principle of antisense oligonucleotide function, the structure of antisense oligonucleotide analogues, the different strategies for improvement of their biological potency, and selected reports on successful in vivo studies and first clinical investigations using these antisense oligonucleotides are discussed.     

Ferroelectric Films

The preparation and properties of ferroelectric films are reviewed. Specific attention is directed to ferroelectric films prepared by wet chemical methods. Emphasis is placed on the microstructure and properties of SBT films for memory applications, and their dependence on chemistry and processing, as well as on the effects of chemistry and processing on the properties of piezoelectric and pyroelectric films. Emphasis is placed on recent results obtained in our laboratories, including modeling of the ferroelectric behavior of films and experimental results in each of these areas. Also considered is the use of ferroelectric films in memory, piezoelectric and pyroelectric devices of various types, with specific note made of the recently-announced use of pyroelectric sensors in automobiles.     

Creep of Single Crystals – Modelling and Numerical Aspects

A number of constitutive models, utilizing both microstructural and/or phenomenological considerations, have been developed for the simulation of the creep behaviour of nickel-base single crystal superalloys at elevated temperatures. In this work, emphasis is placed on the rate-dependent single crystal plasticity model [1]. A strategy for the identification of the material parameters of the model to fit the results from experiments has been implemented. The parameter fitting methodology rests upon a two-membered evolution strategy. In addition, a proposal is made for the extension of the Cailletaud model [1] by means of an evolution equation for a damage variable which enables the modelling of the tertiary creep stage. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

3D modeling of discrete impurity effects in silicon quantum dots: energy level spacing and scarring effects

We present simulation results obtained using a 3D coupled Schrödinger–Poisson equation solver. Of special interest in this work were the effects that discrete impurities have on the energy spectra in the dot and how these effects can be used to better explain conductance peaks observed in experimental measurements. We also explored the behavior of the energy level separations in the closed quantum dot system, observing indications of the onset of chaos.     

Oxidation of 2-mercaptobenzoxazole in aqueous solution: solid phase formation at glassy carbon electrodes

The redox reactions of 2-mercaptobenzoxazole (MBO) have been investigated by cyclic voltammetry at glassy carbon electrodes in aqueous solution. Four anodic and three cathodic processes could be identified. A more detailed analysis of the oxidation processes up to a potential of +0.6 V (SCE) and the corresponding reduction signals showed that the oxidation leads to bis(benzoxazolyl) disulfide (BBOD). Owing to its low solubility, the oxidation product remains at the electrode surface. This product has been identified by ex situ FTIR and XPS analysis. During the reduction of BBOD, mainly MBO is formed. The remarkable lower solubility of BBOD in aqueous solutions compared to MBO allows preparation of layers of BBOD in situ and to control the amount of deposited BBOD via the MBO solution concentration and electrolysis time. The peak potential and peak shape of the reduction signals change remarkably as the amount of BBOD increases from submonolayer coverage to coverages that correspond to multilayers. The behavior can be explained by assuming an electrochemical conversion of BBOD microcrystals, which are deposited on the electrode surface, if the amount of BBOD formed during the MBO oxidation exceeds one monolayer. Received: 21 January 1999 / Accepted: 15 March 1999     

Analytische Untersuchungen zum Small-Scale-Yielding-Problem

In connection with the asymptotic solution of HUTCHINSON for the small scale yielding problem in a power-law hardening material a second approximation is given by a perturbation theory. The method used makes it possible to estimate further approximations in a successive manner. For this purpose an expression is formulated representing the exponents of these approximations.