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.     

AFM observation of polyethylene single crystals: selective handedness of screw dislocations in a chair type

The three-dimensional morphology of polyethylene single crystals grown from dilute solution has been examined by atomic force microscopy. Single crystals were deposited on a soft ground of aqueous solution of poly(vinyl alcohol) (PVA) to avoid the collapse of thin lamellar crystals with thickness of 10 nm. The observation of single crystals on dried PVA clarifies the morphology of a chair type crystal as well as well-known hollow pyramidal type. It has been confirmed that the screw dislocations in the chair type follow a selection rule of the handedness in a manner to relieve the distortion in the chair type.     

Sorption and permeation of iodine in water-swollen poly(vinyl alcohol) membranes and iodine complex formation

The sorption and the permeation of iodine in water-swollen poly(vinyl alcohol) (PVA) membranes and the formation of PVA–iodine complexes were studied. The logarithms of the permeability and the diffusion coefficient decreased approximately linearly with the increase in polymer volume fraction. When the membrane was soaked in an aqueous I₂–KI solution, it contracted and Young's modulus increased. These findings were explained in terms of the formation of extra junction points due to the PVA–iodine complexes. These changes were reversible and could be recovered by replacing the solution with water. The length of the polyiodine chain increased with the increase in the degree of hydration of the membrane. At a fixed degree of hydration, Young's modulus of an iodine-sorbed membrane was much greater than that of a membrane soaked in pure water. This finding was explained on the basis of a double-network structure. The extension of the membrane promoted the complex formation, and the complex disappeared when the tension was released. The critical strain necessary for the complex formation was independent of the degree of hydration. The length of polyiodine chain increased with strain and became constant at higher strains.     

Electrical properties of diphenyldiacetylene annealed under elevated pressure

A unique class of conjugated compounds composed of the derivative of condensed polycyclic aromatic compound with the phenyl group and diphenyldiacetylene oligomer was synthesized by annealing of diphenyldiacetylene under elevated pressure. The effect of annealing pressure on the conductivity of the compounds was studied. The total conductivity of the compound decreased with a decrease of frequency, approaching a constant value (dc conductivity: C_dc). The dc conductivity of the compound increased from below 10^?15 to 10 S cm^?1 with increasing annealing pressure. The dc conductivity of the oligomer was below 10^?15 S cm^?1 and that of the derivative increased from 10^?8 to 10 S cm^?1 with decreasing H/C (H/C:0.45–0.04). The conduction of the conjugated compound was electronic. The temperature coefficient of those dc conductivities was positive, with an approximately linear relation between In (C_dcT^0.5) and (1/T)^0.25, where T is the temperature. The ac conductivities C_ac were proportional to temperature and frequency f and had the following equation C_ac = Tf^S, S = 0.67–0.75. These results showed that the conduction mechanism can be explained by the hopping in a manifold of states at the Fermi level. © 1994 John Wiley & Sons, Inc.     

Thermal shock resistance of flat plastic integrated circuit packages

Flat packages (FPs) were formed from epoxy molding compounds with various physical properties using a transfer molding machine. The compounds were prepared by changing kinds and amounts of additives and addition methods. The thermal shock test was carried out by the following procedures. The plastic package was soaked alternately in liquid nitrogen (?196°) and in liquid solder (200°) in the cycle of 140s. The median life to crack initiation was defined to be the cycles when half of the specimens exhibited crack initiation. According to linear fracture mechanics, the following expression was obtained relating the median life N, thermal stress σ_t, and strength σ_b; N = C/σ·(σ_b/σ_t)^m. We found the linear relation between logarithm of Nσ and logarithm of σ_b/σ_t for various packages, and estimated the values of C and m as 5 × 10⁴ MPa² and 5.5, respectively. The value of m was the same as that obtained for a dual-in-line package.     

Continual conversion of free fatty acid in rice bran oil to triacylglycerol by immobilized lipase

Rice bran oil containing 30–50% free fatty acid was continually converted to an oil containing more than 75% of triacylglycerol (TG) by means of immobilized lipase. The reaction was carried out at 60°C for 24 h with dehydration and reactant mixing by dry nitrogen flow under a positive nitrogen atmosphere. Enzymatic TG synthesis with evaporation by heating was not suitable because of the increasing peroxide value of the oil. Part of this article was presented at the annual meeting of the Japan Oil Chemists' Society at Sendai, Japan, October, 16, 1990.     

Inchworm robot grippers for clothes manipulation

Manipulating deformable objects like clothes, plastic, and paper by a robot is very challenging. This paper focuses on clothes manipulation as an example. A tracing manipulation method is used here to find a corner of the clothes. In this paper, tracing refers to tracing the clothes’ edge, with the robot’s movement based on feedback from sensors. One difficulty during this edge tracing is to make the robot trace smoothly and speedily without dropping the clothes in the process. This is due to the fact that deformable objects are sensitive to contact forces. A solution to this problem is to design a special robot gripper that can trace the clothes without having to worry about the clothes slipping away. In this paper, the development of inchworm-type grippers is proposed. Two sets of grippers inside a robot hand will allow the robot to trace the clothes more freely because there will always be a gripper firmly holding the clothes at any time. A unique tracing method for towel spreading using the inchworm grippers is also discussed. Experimental results have demonstrated the effectiveness of both the proposed grippers and also the algorithm. This work was presented in part at the 12th International Symposium on Artificial Life and Robotics, Oita, Japan, January 25–27, 2007     

Catalytic effect of bis (cyclopentadienyl) nickel II on the improvement of the hydrogenation-dehydrogenation of Mg-MgH2 system

Bis(cyclopentadienyl) nickel II is one of the best precursors of nickel catalyst which remarkably improved the hydrogen absorption-desorption of Mg–MgH₂ system. The X-ray photoelectron spectroscopy (XPS) and Furrier Transformed Infrared Spectroscopy (FTIR) analyses revealed that bis (cyclopentadienyl) nickel II decomposed into metallic nickel during ball milling with MgH₂. The nickel thus formed has homogeneously doped over the Mg - MgH₂ surface. The Ni-doped Mg-MgH₂ have shown the excellent catalytic effect on hydrogen absorption-desorption. The catalyzed MgH₂ could desorb hydrogen below 225 °C (T_onset) under Ar flow, and absorb hydrogen at 50 °C under 1.5 MPa H₂ pressure. The hydrogen absorption-desorption temperatures are remarkably decreased as compared to the uncatalyzed Mg-MgH₂ system under the identical experimental conditions.     

Tuning catalytic performances of cobalt catalysts for clean hydrogen generation via variation of the type of carbon support and catalyst post-treatment temperature

Multi-walled carbon nanotubes, three types of activated carbons, single wall carbon nanotube and reduced graphene oxides were used to synthesize nano-sized Co catalysts for H₂ preparation via NH₃ decomposition. Catalyst samples were characterized by number of techniques such as N₂ physisorption, X-ray diffraction (XRD), X-ray photoelectron spectroscopes (XPS), Transmission electron microscopy (TEM), CO chemisorption, temperature-programmed reduction (H₂-TPR) and temperature-programmed desorption (N₂-TPD). The catalytic activities of the studied catalysts for H₂ production via NH₃ decomposition were measured in a fixed-bed micro-reactor. Co catalyst supported on multi-wall carbon nanotubes has shown the highest catalytic activity. The Co particles size was significantly affected by the variation of the post-treatment temperature. The Co particles size in the range of 4.7–64.8 nm can be effectively controlled by varying post-treatment temperature between 230 and 700 °C. The maximum TOF of NH₃ decomposition was registered on cobalt catalyst post-treated at 600 °C.