Branched‐Tail Lipid Nanoparticles Potently Deliver mRNA In Vivo due to Enhanced Ionization at Endosomal pH

The potential of mRNA therapeutics will be realized only once safe and effective delivery systems are established. Unfortunately, delivery vehicle development is stymied by an inadequate understanding of how the molecular properties of a vehicle confer efficacy. Here, a small library of lipidoid materials is used to elucidate structure–function relationships and identify a previously unappreciated parameter—lipid nanoparticle surface ionization—that correlates with mRNA delivery efficacy. The two most potent materials of the library, 306O₁₀ and 306O_i10, induce substantial luciferase expression in mice following a single 0.75 mg kg^?1 mRNA dose. These lipidoids, which have ten‐carbon tails and identical molecular weights, vary only in that the 306O₁₀ tail is straight and the 306O_i10 tail has a one‐carbon branch. Remarkably, this small difference in structure conferred a tenfold improvement in 306O_i10 efficacy. The enhanced potency of this branched‐tail lipidoid is attributed to its strong surface ionization at the late endosomal pH of 5.0. A secondary lipidoid library confirms that O_i10 materials ionize more strongly and deliver mRNA more potently than lipidoids containing linear tails. Together, these data highlight the exquisite control that lipid chemistry exerts on the mRNA delivery process and show that branched‐tail lipids facilitate protein expression in animals.     

Fatigue Performance of Friction-Stir-Welded Al-Mg-Sc Alloy

Fatigue behavior of a friction-stir-welded Al-Mg-Sc alloy was examined in cast and hot-rolled conditions. In both cases, the joints failed in the base material region and therefore the joint efficiency was 100 pct. The specimens machined entirely from the stir zone demonstrated fatigue strength superior to that of the base material in both preprocessed tempers. It was shown that the excellent fatigue performance of friction-stir joints was attributable to the ultra-fine-grained microstructure, the low dislocation density evolved in the stir zone, and the preservation of Al₃Sc coherent dispersoids during welding. The formation of such structure hinders the initiation and growth of fatigue microcracks that provides superior fatigue performance of friction-stir welds.     

A multilevel longitudinal study of experiencing virtual presence in adolescence: the role of anxiety and openness to experience in the classroom

Presence describes the feeling of reality and immersion that users of virtual/Internet environments have. Importantly, it has been suggested that there are individual and contextual differences regarding susceptibility to presence. These aspects of presence have been linked to both beneficial and disadvantageous uses of the Internet, such as online therapeutic applications and addictive Internet behaviours. In the present study, presence was studied in relation to individual anxiety symptoms and classroom-level openness to experience (OTE) using a normative sample of 648 adolescents aged between 16 and 18 years. Presence was assessed with the Presence II questionnaire, anxiety symptoms with the relevant subscales of the SCL-90-R, and OTE with the Five-Factor Questionnaire. A three-level hierarchical linear model was calculated. Results showed that experiencing presence in virtual environments dropped between the ages of 16 and 18 years. Additionally, although anxiety symptoms were associated with higher presence at 16 years, this association decreased with age. Results also demonstrated that adolescents in classrooms higher on OTE reported reduced level of experiencing presence. The practical and theoretical implications of these findings are discussed.     

Projection method of resolving ambiguities by determining the order of colors in moiré fringes

From the scientific literature there are some well-known methods used to resolve the arising problem of ambiguities in moiré patterns. The main disadvantage of these methods is that for image processing one must use several patterns. It means that it is impossible to work with dynamic objects in a real-time operation mode. We present a projection method to resolve ambiguities by determining the order of colors in moiré patterns. This method is based on the application of color rulings to gratings in a projection moiré technique.     

High-contrast images of semiconductor sites via one-photon optical beam-induced current imaging and confocal reflectance microscopy

We demonstrate a computationally efficient procedure for determining only the semiconductor sites in a confocal reflectance image of an integrated circuit. It utilizes a one-photon optical beam-induced current (1P-OBIC) and confocal reflectance images that are generated from the same focused excitation beam. A 1P-OBIC image is a two-dimensional map of the currents induced by the beam as it is scanned across the circuit surface. A 1P-OBIC is produced by an illuminated semiconductor material if the excitation photon energy exceeds the bandgap. The 1P-OBIC image has no vertical resolution because the 1P-OBIC is linear with the excitation beam intensity. The exclusive high-contrast image of semiconductor sites is generated by the product of the 1P-OBIC image and the confocal image. High-contrast images of the metal sites are also obtained by the product of the complementary OBIC image and the same confocal image.     

Spatial light modulator-controlled alignment and spinning of birefringent particles optically trapped in an array

We demonstrate the use of a phase-only liquid-crystal spatial light modulator (SLM) for polarization-controlled rotation and alignment of an array of optically trapped birefringent particles. A collimated beam incident upon a two-dimensional lenslet array yields multiple foci, scaled to produce optical gradient traps with efficient three-dimensional trapping potentials. The state of polarization of each trapping beam is encoded by the SLM, which acts as a matrix of wave plates with computer-controlled phase retardations. Control of the rotation frequency and alignment direction of the particles is achieved by the transfer of tunable photon spin angular momentum.