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.     

Thermal Bending Analysis of Doubly Curved Composite Laminated Shell Panels with General Boundary Conditions and Laminations

Thermal bending analysis of doubly curved laminated shell panels with general boundary conditions and laminations is presented. The equations of equilibrium are derived in the form of two coupled sets of ordinary differential equations based on a general shell theory and solved through the state-space approach in a repeated manner. It is depicted that the results of the present method are in great agreement with analytical solutions. Cylindrical shell panels with general boundary conditions and laminations, where no analytical solution is available, are solved. It is found that the present method exhibits a high convergence rate as well as presenting accurate results in all cases.     

Soret and Dufour effects between two rectangular plane walls with heat source/sink

This study addresses the thermo‐diffusion and the diffusion‐thermo phenomena in a semi‐infinite absorbent channel whose walls are contracting/expanding, with heat source/sink effects. The governing partial differential equations with suitable boundary conditions are transformed to a system of dimensionless ordinary differential equations. An analytic solution of the problem has been found using a technique called homotopy analysis method (HAM). HAM gives consistently valid answers to the problem over an extensive variety of parameters and also provides better accuracy. To validate the analytical results, a comparison has been presented with a numerical solution calculated by using the parallel shooting method. The effects of dimensionless parameters, that is, deformation parameter, Reynolds number, Soret and Dufour numbers, and heat source/sink parameter on the expressions of velocity, temperature, and concentration profiles are analyzed graphically to understand the physics of the deformable channel. It has been noted that the velocity across the channel is higher for the expanding channel, as compared to that for the contracting channel. Also the Soret and Dufour number increases the temperature of the fluid, and decreases the concentration. The temperature profile has an increasing behavior in the case of heat source, and a decreasing behavior in the case of heat sink.     

Characterization of the Ion Beam Current Density of the RF Ion Source with Flat and Convex Extraction Systems

Silicon - The characterization of ion beam current density distribution and beam uniformity is crucial for improving broad-beam ion source technologies. The design of the broad ion beam extraction...     

Non-chaotic and chaotic propagation of stationary and dynamic images through MVKS turbulence

Anisoplanatic electromagnetic (EM) propagation across a turbulent atmosphere has been recently examined for an unmodulated carrier propagating over an image-bearing transparency through optical lensing, and for the embedded information inside a carrier recovered using heterodyning and digital demodulation. Carrier modulation yielded better recovery than simple lens-based imaging. A possible mitigation strategy is proposed whereby the image information is encrypted on an RF chaotic carrier, thereafter secondarily embedded onto an optical carrier. Results based on the modified von Karman (MVKS) and the Hufnagel-Valley (H-V) models showed that the signal/image recovery under turbulence is improved compared with non-chaotic propagation. The case of time-varying/dynamic images is also taken up; it is demonstrated via cross-correlation products that turbulence is mitigated by the use of chaotic carrier encryption. Overall, transmission via chaos offers mitigation against distortions due to turbulence along with the security feature inherent via the chaos keys which prevent signal recovery without key-matching.     

Influence of Different Additives on the Interaction of Quinolone Antibiotic Drug with Surfactant: Conductivity and Cloud Point Measurement Study

Conductometric and cloud point (CP) measurement studies have been performed to investigate the interaction of tetradecyltrimethylammonium bromide (TTAB) and Triton® X-100 (TX-100) with ciprofloxacin hydrochloride (CFH) in different solvents over the temperature range of 295.15–315.15 K. CFH is used for the treatment of various bacterial infections. The observed critical micelle concentration (CMC) values of TTAB were found to be reduced in the presence of electrolytes (Na₂SO₄/Na₃PO₄), and this reduction proceeds with the elevation of salt concentration. The order of the CMC of TTAB follows the trend: > >. The observed CMC values of TTAB were found to increase with increasing temperature and decrease with increasing concentration of CFH in aqueous medium. The values of Gibbs free energy of micellization () for the TTAB/TTAB + CFH mixture were found to be negative, implying spontaneous micellization. The estimated CP of TX-100 decreases with increasing concentration of TX-100 in aqueous medium. The CP values first decrease with increasing concentration of CFH and then increase at higher concentration of CFH almost in all cases investigated. The values of free energy of clouding were found to be positive in all cases studied implying that phase separation of TX-100 was nonspontaneous. The other thermodynamic parameters associated with the micellization of TTAB and the phase separation of TX-100 were estimated and explained.