Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Determination of the uranium enrichment with the NaIGEM code

The traditional method used to non-destructively determine the uranium enrichment with an NaI detector is based on the “enrichment meter principle” (Progress report LA-4605-MS, Los Alamos National Laboratory, NNM, 1970, p. 19), which involves measuring the intensity of the 186 keV line of ²³⁵U by selecting two regions of interest for the peak and the background. This type of method suffers from several limitations, the most limiting of which are the impossibility to make wall thickness correction or to take the inference of foreign radioisotopes into account. The NaIGEM software (A guide for using NaIGEM code, version 1.5 for DOS and Windows, 2001; Nucl. Instr. and Meth. A 458 (2001) 196) was developed to overcome these limitations by calculating the 186 keV line intensity with a fitting procedure. The code was tested in different measurement conditions on the wide variety of certified samples, in particular, on reprocessed uranium and on depleted material with thick steel filters interposed between the source and the detector. The results are presented to illustrate the performance and limitations of the tested version (A guide for using NaIGEM code, version 1.5 for DOS and Windows, 2001). The general performance is good except in the case of low-enriched uranium in thick containers.     

Electrical characteristics of the ITO/HgInTe photodiodes

Photodiodes designed to be sensitive in the region 0.5–1.7 μm and obtained by vacuum magnetron sputtering of the ITO (SnO₂ + In₂O₃) layer on the surface of the Hg₃In₂Te₆ single crystal are studied. The electrical characteristics, measured at 265–333 K, indicate that the mechanism of charge transport in the diodes under study is thermionic. The current-voltage characteristic and its temperature variations are described quantitatively based on the energy diagram and the found parameters of the heterojunction. Original Russian Text ? L.A. Kosyachenko, I.M. Rarenko, E.F. Sklyarchuk, I.I. German, Sun Weiguo, 2006, published in Fizika i Tekhnika Poluprovodnikov, 2006, Vol. 40, No. 5, pp. 568–571.     

Keine Mautdaten für Ermittlungsverfahren

Das Autobahnmautgesetz zeichnet sich durch eine strenge Zweckbindung für die Mautdaten aus. Diese dürfen ausschlie?lich für die Zwecke des Mautgesetzes erhoben und verarbeitet werden. Diese Vorgabe hat das LG Magdeburg in einem Beschluss richtungsweisend auch für die Verbindungsdaten der GSM-Kommunikation best?tigt.     

Defect-free sintering of two material powder injection molded components Part II Model

A defect-free, two-material component can be obtained via co-sintering by suitably altering the powder characteristics or compositions, as demonstrated in Part I. In this paper, a model to ascertain the suitability of material systems to be co-sintered without defects such as delamination or interface pores is presented. The model is based on the management of the stress induced due to the difference in shrinkage and an analysis of the in situ strength of the weaker material during sintering. Tool steel in combination with stainless steel admixed with boron and Fe-2Ni admixed with boron are two systems used to validate the model. The predictions of the model are in good agreement with the observations.     

High-cycle fatigue monitoring in AgClxBr1-x fibres using absorption spectroscopy

The spectral transmittance of mixed silver-halide polycrystalline fibres was measured while they were undergoing repeated bending leading to mechanical fatigue. Microscopic mechanical defects were detected through their influence on the optical losses, without interfering with the deformation. Optical and mechanical lifetimes of the fibres were found to depend on the composition and to be larger for highly-mixed compositions. Scanning electron microscopy observations of fatigued fibres revealed a strong influence of the fibre composition on the fatigue damage. This dependence on the composition was explained using a theoretical model of solid-solution strengthening. This revised version was published online in November 2006 with corrections to the Cover Date.     

Master sintering curve concepts as applied to the sintering of molybdenum

Sintering experiments with various molybdenum powders are rationalized using a master sintering curve concept that collapses density, grain size, or other parameters onto a single curve. In this case, the integral work of sintering is developed and customized for different green densities. Construction of the master sintering curve is described to show how the curve can be normalized with respect to green density effects. Various grades of molybdenum for metal injection molding and die compaction are included in the analysis, processed over a range of heating cycles. Die-compacted samples of varying green densities are used to illustrate the efficacy of the new, normalized master sintering curve concept. Sintering cycle optimization is one possible outcome from this analysis.