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.     

A slotted post-wall waveguide array with interdigital structure for 45/spl deg/ linear and dual polarization

This work proposes a dual-polarized planar antenna; two post-wall slotted waveguide arrays with orthogonal 45/spl deg/ linearly-polarized waves interdigitally share the aperture on a single layer substrate. Uniform excitation of the two-dimensional slot array is confirmed by experiment in the 25 GHz band. The isolation between two slot arrays is also investigated in terms of the relative displacement along the radiation waveguide axis in the interdigital structure. The isolation is 33.0 dB when the relative shift of slot position between the two arrays is -0.5/spl lambda//sub g/, while it is only 12.8 dB when there is no shift. The cross-polarization level in the far field is -25.2 dB for a -0.5/spl lambda//sub g/ shift, which is almost equal to that of the isolated single polarization array. It is degraded down to -9.6 dB when there is no shift.     

An analysis of a waveguide T junction with an inductive post

The authors analyze the T junction with an inductive post, taking its diameter into account for the case where the current distribution is assumed on the surface of the post. A single cylindrical post placed in a T junction improves the impedance matching and compensates the junction discontinuity in a wide frequency band. The effects of the design parameters, such as the diameter of the post and its location, are clarified. The measured return loss is accurately predicted. On the basis of this analysis, an effective design procedure for the T junction is proposed, and the reflection below -30 dB is realized over 4% bandwidth     

Oxyphilic cell variant of endometrioid adenocarcinoma

A case of oxyphilic cell variant of endometrioid adenocarcinoma is presented. To the best of our knowledge, there have been only three such cases reported in the English literature. The patient was a 35-year-old Japanese female (gravida 0, para 0). She was slightly obese with profuse vaginal bleeding. Histological examination of the resected uterus revealed endometrioid adenocarcinoma with an exclusive oxyphilic cell component. There was no evidence of myometrial invasion nor lymph node metastases. Reported cases of oxyphilic cell variant of endometrioid adenocarcinoma, including the present case, were stages 0-1 and grades 1-2. Although further study is necessary to evaluate this variant, oxyphilic cell variant seems to be an early stage of adenocarcinoma and should be differentiated from eosinophilic metaplasia and other types of adenocarcinoma of the endometrium.     

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.     

Spectral transmittance of organic dye-doped glass films obtained by the solgel method

The spectral transmittance of colored glass films synthesized by the solgel method is presented. The film was formed on a glass slide by dipping it into an organic dye-doped solution and, thereafter, by putting it into a furnace for solidification. Three dyes, Methylene Blue, Eosin, and Uranine, were used that exhibit transparent blue, pink, and yellow colors, respectively, when they are dissolved in the starting solution. We clarify how the spectral transmittance of the films varies with the solidification temperature. The films doped with two of the three dyes that exhibit violet, orange, and green colors are also synthesized, and their transmittance is measured. Moreover, the chemical durability of the films and the transmittance change caused by aging and illumination are examined.