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.     

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.     

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)     

Prediction of slip resistance in climbing systems

The objective of this study was to develop a predictive model describing the slip resistance of various climbing surfaces. In a four-factor experiment, seven commonly used metal grating step surfaces were evaluated, along with four types of shoe soles (crepe, leather, ribbed-rubber, and oil-resistant-rubber); three contaminant conditions (dry, wet-water, and diesel fuel); and direction of force application. The results showed that the available slip resistance coefficients (ASRC) varied primarily as a function of sole material and contaminants. This result and the significant interactions between sole and step surfaces suggest that the appropriate selection of shoe soles and control of contaminants may be the most effective way of attaining adequate ASRC values. A predictive equation was developed using multiple regression which described the evaluated conditions with binary indicator variables. To increase the equation's applicability, the step surfaces were described in terms of generic features such as: painted vs. bare metal surface; ring vs. point protrusions; edge orientation; contact area, and protrusion height gradient. The equation explained 89% of the variance in the original data. In a validation study, the equation explained 80% of the variance in slip resistance for a new step surface under the original set of sole, contaminant, and directionality conditions.     

Activation of phospholipase C gamma by PI 3-kinase-induced PH domain-mediated membrane targeting

Signaling via growth factor receptors frequently results in the concomitant activation of phospholipase C gamma (PLC gamma) and phosphatidylinositol (PI) 3-kinase. While it is well established that tyrosine phosphorylation of PLC gamma is necessary for its activation, we show here that PLC gamma is regulated additionally by the lipid products of PI 3-kinase. We demonstrate that the pleckstrin homology (PH) domain of PLC gamma binds to phosphatidylinositol 3,4,5-trisphosphate [PdtIns(3,4,5)P3], and is targeted to the membrane in response to growth factor stimulation, while a mutated version of this PH domain that does not bind PdtIns(3,4,5)P3 is not membrane targeted. Consistent with these observations, activation of PI 3-kinase causes PLC gamma PH domain-mediated membrane targeting and PLC gamma activation. By contrast, either the inhibition of PI 3-kinase by overexpression of a dominant-negative mutant or the prevention of PLC gamma membrane targeting by overexpression of the PLC gamma PH domain prevents growth factor-induced PLC gamma activation. These experiments reveal a novel mechanism for cross-talk and mutual regulation of activity between two enzymes that participate in the control of phosphoinositide metabolism.