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.     

Using aspects for testing of embedded software: experiences from two industrial case studies

Aspect-oriented software testing is emerging as an important alternative to conventional procedural and object-oriented testing techniques. This paper reports experiences from two case studies where aspects were used for the testing of embedded software in the context of an industrial application. In the first study, we used code-level aspects for testing non-functional properties. The methodology we used for deriving test aspect code was based on translating high-level requirements into test objectives, which were then implemented using test aspects in AspectC++. In the second study, we used high-level visual scenario-based models for the test specification, test generation, and aspect-based test execution. To specify scenario-based tests, we used a UML2-compliant variant of live sequence charts. To automatically generate test code from the models, a modified version of the S2A Compiler, outputting AspectC++ code, was used. Finally, to examine the results of the tests, we used the Tracer, a prototype tool for model-based trace visualization and exploration. The results of the two case studies show that aspects offer benefits over conventional techniques in the context of testing embedded software; these benefits are discussed in detail. Finally, towards the end of the paper, we also discuss the lessons learned, including the technological and other barriers to the future successful use of aspects in the testing of embedded software in industry.     

Hpcfolder: a simple tool used to parallelize algorithms using the message passing interface (MPI)

The Journal of Supercomputing - Hpcfolder is a user-friendly high-performance computing tool that can be used to analyze the performance of algorithms parallelized using MPI. It is possible to view...     

Life cycle energy and carbon footprint analysis of photovoltaic battery microgrid system in India

Electricity supply in India is from a centralized grid. Many parts of the country experience grid interruptions. Life cycle energy and environmental analysis has been done for a 27 kWp photovoltaic system which acts as grid backup for 3 h outage in an Indian urban residential scenario. This paper discusses energy requirements and carbon emission for a PV storage system for five different battery technologies in Indian context. This can be used as a metric for comparative analysis for new batteries, with an undeveloped market. The energy requirements for the components are quantified and are compared in terms of energy payback time (EPBT) and Net Energy Ratio (NER). All the calculations are done for Indian context. EPBT is found to be in the range of 2–4.5 years for all the systems, while NER is in the range of 6.6–2.52. NaS has the highest emission factor of 0.67 kgCO₂/kWh and the least for NiCd (0.091 kgCO₂/kWh). These factors can be used to select a PV battery option and to target selection of materials and systems based on the reported values.     

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.     

Prediction of traditionally utilised wheat dough technological quality parameters from Mixolab values: development and evaluation of regression models

The research was conducted with the aim to investigate the possibility of Farinograph, Extensograph and Amylograph values prediction with linear and/or multiple Mixolab regression models. In total, 163 flour samples were divided based on Machalanobis distances into three sets: prediction, validation and external sample set. Determination coefficients ranged from 0.145 to 0.640 for linear regression models and from 0.279 to 0.739 for multiple regression models. Internal and external validation of developed regression models was conducted. Testing of developed models resulted in a high share of samples for which predicted values were out of the ranges of method official reproducibility and a high share of samples for which predicted values were out of the quality level range obtained by analytical measurement. It was concluded that it is impossible to develop applicable regression models for prediction of Farinograph, Extensograph and Amylograph parameters on the basis of Mixolab values from standard protocol.     

Structure formation mechanisms in consolidating pigment coatings—Simulation and visualisation

Microstructure development in consolidating pigment coating layers was studied in terms of particle flocculation and clustering mechanisms utilising a 3D particle dynamics model. The model includes hydrodynamic forces, colloidal interactions as well as the Brownian motion. The influence of colloidal interactions and drying strategy on the coating layer thickness development and internal solid concentration gradients, was investigated. A low particle surface potential resulted in the formation of porous particle networks, which impeded the shrinkage of the coating layer. At higher surface potentials particles arranged into denser structures, whereby the solids concentration profile could be controlled by the drying. Low electrostatic double layer thicknesses allowed sharp concentration gradients to form as result of the applied drying strategy. At high double layer thicknesses, the structure formation was similar regardless of drying strategy. This work elucidates the combined effect of drying conditions and colloidal suspension properties on coating microstructure development. Furthermore, the results aid in the understanding of how coating suspension additives may influence the structure development of the coating layer.