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.     

Antenna phase pattern measurements at millimeter wave frequencies using the differential phase method with only one power meter

The differential phase measurement method has been improved to need the use of only one power meter instead of three power meters. This enables accurate antenna phase pattern measurements with a simplified set-up, accompanied by the reduction in cost. All advantages of the differential phase measurement method are still also available, e.g. there is no need to phase lock oscillators or to use rotary joints. The measurement results for an antenna at 110 GHz are presented. A good agreement with earlier data was obtained.     

A signal-detection theory based perspective on design of warning

The effects of warnings are analyzed using a distributed signal-detection theory model. It is established that selectivity always increases effectiveness. The implications to optimal warning design for intermittent versus continuous hazards are discussed. The changes in the behavior of the 6 human subjects in response to changes in the warning levels are consistent with the predictions of the model.     

The effect of damming on biological quality according to macroinvertebrates in some Estonian streams,Central—Baltic Europe: A pilot study

The effect of damming on the structure of the macroinvertebrate community and biological quality was studied in nine (the 3–6th order) lowland streams of Estonia, Central—Baltic ecoregion of Europe. Four habitats—reservoirs with accumulated fine sediments, reservoirs with hard bottom, and two corresponding below‐dam areas (both fast‐flowing)—were compared to study whether and how significantly the bottom substrata in dammed areas affected macroinvertebrates and biological quality downstream of dams. The standard kick‐net samples (1.25 m², complemented with qualitative sample) were collected in autumn 2005—spring 2006. The multimetric biological quality, based on five macroinvertebrate indices (total taxa richness, EPT taxa richness, Average Score Per Taxon, Danish Stream Fauna Index, Shannon diversity) was estimated and compared with reference values. Biological quality in reservoirs with hard bottom and their downstream reaches corresponded to good, or even high quality. Conversely, damming affected biological quality significantly and negatively, above the dam if fine sediments were accumulated. The effect was the strongest within muddy reservoirs themselves (revealing moderate quality only). However, some harmful consequences of mud were observed also downstream of dams. The results also demonstrated that the indices of estimation of organic pollution and/or general quality were able to reflect significant changes in stream flow. Copyright © 2010 John Wiley & Sons, Ltd.     

Semiautomated Identification and Classification of Customer Complaints

This paper examines the feasibility of extracting useful information from customer comments using a Naïve Bayes classifier. This was done for a database, obtained from a large Korean mobile telephone service provider, of 533 customer calls to call centers in 2009. After eliminating calls not containing customer complaints or comments, the remaining 383 comments were classified by an expert panel into four domains and 27 complaint categories. The four domains were Transaction‐related (189 comments, 49%), Product‐related (120 comments, 31%), Customer Service or Support‐related (38 comments, 10%) and Customer Outreach and Marketing‐related (36 comments, 9%). The comments were then randomly assigned to either a training set (257 cases, 67%) or test set (126 cases, 33%). The training set was used to develop a Naïve Bayes classifier that correctly predicted the domain 75% of the time and the specific subcategory 51% of the time for the test set. Prediction accuracy was strongly related to prediction strength for both sets of predictions, suggesting that simple filtering strategies where difficult to understand comments are flagged for expert review and easy comments are automatically classified are both technically feasible and likely to be practically valuable. Several strong predictors were also identified that corresponded to categories more detailed than those originally assigned. © 2012 Wiley Periodicals, Inc.     

Localization of trehalose in partially hydrated DOPC bilayers: insights into cryoprotective mechanisms

Trehalose, a natural disaccharide with bioprotective properties, is widely recognized for its ability to preserve biological membranes during freezing and dehydration events. Despite debate over the molecular mechanisms by which this is achieved, and that different mechanisms imply quite different distributions of trehalose molecules with respect to the bilayer, there are no direct experimental data describing the location of trehalose within lipid bilayer membrane systems during dehydration. Here, we use neutron membrane diffraction to conclusively show that the trehalose distribution in a dioleoylphosphatidylcholine (DOPC) system follows a Gaussian profile centred in the water layer between bilayers. The absence of any preference for localizing near the lipid headgroups of the bilayers indicates that the bioprotective effects of trehalose at physiologically relevant concentrations are the result of non-specific mechanisms that do not rely on direct interactions with the lipid headgroups.     

Thermal wave imaging through radio frequency induction heating

Radio frequency (RF) induction heating is used in order to generate thermal waves in conducting materials. This technique is applied to measure the thickness of tungsten-carbide plasma coating on stainless-steel plates. The letter briefly discusses major advantages and disadvantages of RF induction heating.     

Short Vapour Residence Time Catalytic Pyrolysis of Spruce Sawdust in a Bubbling Fluidized-Bed Reactor with HZSM-5 Catalysts

Catalytic pyrolysis of spruce sawdust was carried out in a bubbling fluidized-bed reactor using HZSM-5 catalysts. The effects of space velocity, catalyst deactivation, catalyst acidity and catalyst regeneration were studied. The use of catalysts decreased the yield of organic liquids compared to non-catalytic yields while the yields of pyrolytic water and gases increased. Decreasing the space velocity enhanced these effects. The rate of catalyst deactivation depended on the acidity of the catalyst, with more acidic catalysts deactivating more rapidly. Using a catalyst with a Si/Al ratio of 140 resulted in the largest changes in bio-oil properties. Periodic regeneration of the catalyst in the fluidized-bed reactor was also demonstrated using varying regeneration times and temperatures. It was shown that compared to BFB reactors, CFB reactor types would offer better operating characteristics for commercial scale catalytic pyrolysis processes in regard to vapour residence times, and catalyst activity and regeneration.     

A large planar 39-GHz antenna array of waveguide-fed horns

A planar antenna in which box horns are used as radiating elements is described. The feed network is built by connecting rectangular waveguides with T-junctions. The matching of the T-junctions is improved by using rounded splitters and matching pins in the junctions. The radiating element has been designed to cancel out the grating lobe. The grating lobe is due to an element spacing larger than one wavelength. The highest sidelobes are at least 31 dB below the main beam in the H-plane and 16 dB in the E-plane. A gain of 37 dBi has been achieved at 39.2 GHz. These results demonstrate the feasibility of this antenna for applications requiring high gain at millimeter wavelengths     

Predictors and consequences of achievement goals in the college classroom: Maintaining interest and making the grade.

The authors investigated personality predictors of achievement goals in an introductory psychology class, as well as the consequences of these goals for the motivation and performance of 311 undergraduates. Two dimensions of achievement motivation (workmastery and competitive orientations; J. T. Spence & R. L. Helmreich, 1983) predicted the goals endorsed. Individuals high in workmastery were more likely to adopt mastery goals and less likely to adopt work avoidance goals, whereas competitive individuals were more likely to endorse performance and work avoidance goals. Students adopting mastery goals were more interested in the class, but students adopting performance goals achieved higher levels of performance. These results suggest that both mastery and performance goals can lead to important positive outcomes in college classes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)