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.     

Defocusing image to pattern contact holes using attenuated phase shift masks

The patterning of contact holes by selecting out-of-focus image plane (defocus) using attenuated phase shift masks (APSM) has been studied. Defocus is found to enhance the image modulation at low partial coherence for contact holes with negative local average of mask function. Semi-dense holes up to 130 nm in 8% APSM have been printed by 0.5 μm defocus at a partial coherence of 0.31 using KrF scanner with highest numerical aperture of 0.68. However, these holes were closed with in-focus imaging. Defocus is also found to be beneficial for patterning the pitches that have extensive side lobes with in-focus imaging.     

Dynamical modelling of an activated sludge system of a petrochemical plant operating at high temperatures.

The Mexican petrochemical industry, Morelos S.A. de C.V., is one of the biggest and more important petroleum industries in Mexico and Latin America. It has an activated sludge system to treat its wastewater flow, which is approximately 7,000 m3/d. The wastewater contains volatile organic carbon substances classified as toxics. The old surface aeration system was changed for fine bubble diffusers; however, one major drawback of the new aeration system is that the temperature in the bioreactor has increased due to the compression of the air, which at the compressor exit reaches 85 degrees C. This effect results in the temperature in the bioreactor attaining 32 degrees C during the fall, whereas in the spring and summer, the bioreactor temperature reaches higher values than 40 degrees C. The high temperatures reduce the microorganism activity and cause a higher volatilisation rate of volatile compounds, among other effects, which affect the performance of the biological treatment. This work was performed to obtain a better modelling of the wastewater treatment from the petrochemical industry. The model describes the effect of the temperature on the performance of the biological treatment. The model was obtained from tests that were carried out in laboratory reactors with 14 L capacity, which were operated at different temperatures (from 30 to 45 degrees C), with the same wastewater and conditions as the actual system.     

Retaining maximum antioxidative potency of wheat germ oil refined by molecular distillation

A process of physical refining wheat germ oil using the technique of molecular distillation (MD) is presented in this work. Wheat germ oil was obtained from the germ by solvent extraction using hexane and also by cold pressing. The oil extracted with hexane was degummed and bleached before deacidification in order to modify the parameters of phosphorus and color. The goal in carrying out the stage of physical refining by MD was to preserve the maximum amount of original antioxidative potential obtained from extraction of the crude oil. The effect of evaporation temperature of one‐stage MD on the efficiency of free fatty acid elimination was studied. The antioxidant portion was followed by means of analytic determination of tocopherols by high‐performance liquid chromatography. Tocopherol retention up to 98% was achieved in the oil extracted by pressing, and yields of up to 96% were achieved in the oil extracted with hexane. Copyright © 2007 Society of Chemical Industry     

A stochastic realization algorithm via block LQ decomposition in Hilbert space

A stochastic realization problem of a stationary stochastic process is re-visited, and a new stochastically balanced realization algorithm is derived in a Hilbert space generated by second-order stationary processes. The present algorithm computes a stochastically balanced realization by means of the singular value decomposition of a weighted block Hankel matrix derived by a “block LQ decomposition”. Extension to a stochastic subspace identification method explains how the proposed abstract algorithm is implemented in system identification.     

Pedestrian detection and tracking at crossroads

This paper presents a system that can perform pedestrian detection and tracking using vision-based techniques. A very important issue in the field of intelligent transportation system is to prevent pedestrians from being hit by vehicles. Recently, a great number of vision-based techniques have been proposed for this purpose. In this paper, we propose a vision-based method, which combines the use of a pedestrian model as well as the walking rhythm of pedestrians to detect and track walking pedestrians. Through integrating some spatial and temporal information grabbed by a vision system, we are able to develop a reliable system that can be used to prevent traffic accidents happened at crossroads. In addition, the proposed system can deal with the occlusion problem. Experimental results obtained by executing some real world cases have demonstrated that the proposed system is indeed superb.     

An immune oriented multi-agent system for biological image processing

In this article, we present a parallel image processing system based on the concept of reactive agents. Our system lies in the oRis language, which allows to describe finely and simply the agents’ behaviors to detect image features. We also present a method of segmentation using a multi-agent system, and two biological applications made with oRis. The stopping of this multi-agent system is implemented through a technique issued from immunology: the apoptosis.     

Frequency domain identification of Wiener models

This paper proposes a frequency domain algorithm for Wiener model identifications based on exploring the fundamental frequency and harmonics generated by the unknown nonlinearity. The convergence of the algorithm is established in the presence of white noise. No a priori knowledge of the structure of the nonlinearity is required and the linear part can be nonparametric.