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.     

Java multimedia telecollaboration

Using Java-based tools in multimedia collaborative environments accessed over the Internet can increase an application's client base. Most operating systems support Java, and its "compile once-run everywhere" architecture is easy to maintain and update. The Java-based tools presented here let users share Internet resources, including resources originally designed for single use.     

Narrow-band correction of the residual amplitude modulation in frequency-modulation spectroscopy

We have developed a narrow-band controller in the MHz range, based on a field-programmable gate array. It is used to control the probe beam intensity in frequency-modulated spectroscopy experiments with an acoustooptic modulator. The residual amplitude modulation at the modulation frequency (2.5 MHz) is reduced by 50 dB. The first-harmonic detection of the signals is operated in saturation spectroscopy of I/sub 2/ at 514.5 nm and 501.7 nm. A reduction of the background noise and a large increase in the signal-to-noise ratio are obtained.     

Expectations about counseling in Yucatán, Mexico: Toward a "Mexican psychology."

Conducted a study of client expectations of psychological services in Yucatán, Mexico, under the sponsorship of a grant from the Organization of American States. The Expectations about Counseling–Brief form (EAC-B) questionnaire was translated and administered to 488 subjects across age, sex, and experience with psychological services. Subsequent analyses supported the reliability and robustness of the Spanish EAC-B, with factor structure similar to the EAC-B in English. Some relation was found among age, sex, prior counseling experience, and expectations about counseling. Implications of these data for future research and comparison with U.S. subjects are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Theory of correlations in partly labelled homopolymer melts

Small-angle neutron scattering by a polymer melt with partly tagged chains is considered. When several types of chain (differently labelled) are present in the system a new long-range correlation effect which modifies the scattering spectrum is predicted. This effect will arise because of the chemical polydispersity of the sample. A general formalism is developed to calculate the scattering intensity and is applied to special cases: diblock and triblock chains. It is shown that even a small chemical polydispersity leads to important long-range fluctuations and modifies the scattering spectrum substantially.     

Extrapolation of fuzzy values from incomplete data bases

This paper presents different approaches which enable a data base management system to obtain a plausible fuzzy estimate for an attribute value of an item for which the information is not explicitly stored in the data base. This can be made either by a kind of analogical reasoning from information about particular items or by means of expert rules which specify the (fuzzy) sets of possible values of the attribute under consideration, for various classes of items. Another kind of expert rules enables the system to compute an estimate from the attribute value of another item provided that, in other respects, this latter item sufficiently resembles the item, the value of which we are interested in; then these expert rules are used either for controlling the analogical reasoning process or for enlarging the scope of application of the first kind of expert rules. The different approaches are discussed in the framework of possibility theory.