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)     

Fuzzy Learning of Talbot Effect Guides Optimal Mask Design for Proximity Field Nanopatterning Lithography

Processing methods used in photonics and nanotechnology possess many limitations restricting their application areas such as high cost, inability to produce fine details, problems with scalability, and long processing time. Proximity field nanopatterning is a lithography method which surpasses these limitations. By using interference patterns produced by a two-dimensional phase mask, the technique is able to generate a submicron detailed exposure on a millimeter-size slab of light sensitive photopolymer, which is then developed like a photographic plate to reveal three-dimensional interference patterns from the phase mask. While it is possible to use simulations to obtain the interference patterns produced by a phase mask, realizing the mask dimensions necessary for producing a desired interference pattern is analytically challenging due to the intricacies of light interactions involved in producing the final interference pattern. An alternative method is to iteratively optimize the phase mask until the interference patterns obtained converge to the desired pattern. However, depending on the optimization technique used, one either risks a significant probability of failure or requires a prohibitive number of iterations. We argue that an optimization technique that is to take advantage of the physics of the problem using machine learning methods (here fuzzy learning) can lead to competent mask design. This technique is described in this letter.