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.     

Metastable phase relation and phase equilibria in the Cr2O3-Fe2O3 system

In order to ascertain the metastable phase relation in the Cr₂O₃-Fe₂O₃ system, the existing phases were investigated by X-ray analysis using samples obtained by heating the coprecipitated powders for 1 h at 600–1000°C. There was a metastable two-phase region of Cr₂O₃-rich (CC) and Fe₂O₃-rich (FC) phases below about 940°C. Equilibrium state of 1:1 composition at 600–900°C was considered to be a single phase of the corundum solid solution. The metastable two-phase CC + FC region was suggested to appear probably due to the compositional inhomogeneity in the coprecipitated powders.     

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.     

Neurochemical studies of schizophrenia in Japan

Neurobiological research in schizophrenia has been hampered by several confounding factors such as the heterogeneity of the illness and the paucity of biological markers. Recent progress in research methods, however, has enabled the improvement in our understanding its pathophysiology. This paper reviews recent neurochemical investigations of schizophrenia and its animal models which were conducted in Japan in the last decade. The research areas reviewed are (i) monoamine and their metabolites in body fluids, (ii) phospholipids and prostaglandins, (iii) neurochemistry in autopsy brains, (iv) immunological measures, (v) magnetic resonance spectroscopy, (vi) regional cerebral blood flows (rCBF), (vii) molecular genetics, and (viii) animal models. It is worth noting that there exist abnormalities of amino acidergic (glutamatergic and GABAergic) neurotransmission as well as monoaminergic (dopaminergic and serotonergic) one in postmortem schizophrenic brains. These abnormalities and also the findings of altered rCBF indicate the existence of disturbed neuronal circuits that contribute to the diverse symptoms of schizophrenia. Also, dysfunction of membrane phospholipids derived from studies on magnetic resonance spectroscopy may underlie negative symptoms in schizophrenia. Given that schizophrenia is considered to comprise a group of disorders with a diverse heterogeneity of etiologies, research in the next decade is expected to identify putative genes that are involved in vulnerability to schizophrenic phenotype.     

Diagnosis of childhood BK virus cystitis by electron microscopy and PCR

A case of BK virus cystitis in a 5 year old boy is reported. This patient, who was not immunocompromised, had had acute cystitis for two weeks. Many intracytoplasmic inclusions were observed in urinary sediment smears stained by the Papanicolaou method. Electron microscopic examination showed virus particles, presumed to be human polyomavirus, in the nuclei of the degenerated urothelial cells. A DNA sequence of the BK virus was detected in 200-300 urothelial cells in Papanicolaou stained smears by the polymerase chain reaction. BK virus is an unusual cause of symptomatic cystitis in a healthy child.     

A video DSP with a macroblock-level-pipeline and a SIMD typevector-pipeline architecture for MPEG2 CODEC

A video DSP with macroblock-level-pipeline and a SIMD type vector-pipeline architecture (VDSP2) has been developed, using 0.5 μm triple-layer-metal CMOS technology. This 17.00 mm×15.00 mm chip consists of 2.5 M transistors, and operates at 100 MHz. The real-time encoder and decoder specified in the MPEG2 main profile at the main level can be realized with two VDSP2's and a motion estimation (ME) unit, and one VDSP2 respectively, at an 80 MHz clock rate, with a total power dissipation of 4.2 W at 3.3 V     

Surface Hardening of Carbon Steel Using High Powered YAG Laser

A high powered YAG laser with kaleidoscope for surface modification was applied to the surface hardening of carbon steels containing 0. 18-0.54 wt% C without the absorbents, and the relationships between laser processing and surface hardening were investigated by hardness and microstructure. The structure of the hardened zone underwent complete martensitic transformation in all of the carbon steels tested, and its hardness increased with greater carbon content. Under identical irradiated conditions, the hardened zone expanded with increasing carbon content. A hardened zone extending from the surface to a depth of 1.0 mm was obtained at a laser power of 1.0 kW and a scanning speed of 1 mm/sec. It was found that in the surface hardening of carbon steels, a high powered YAG laser can be used to control the hardened zone by selecting the appropriate irradiation conditions, however, the hardened zone was affected by the assistant gas and the flow rate.     

Dynamic properties of carbon black filled chlorinated polyethylene/hindered phenol blends

Aggregates of carbon black (CB) in a polymer matrix have a tendency to form a CB network. The dynamic mechanical properties of binary systems of chlorinated polyethylene (CPE) and CB or 3,9‐bis{1,1‐dimethyl‐2[β‐(3‐tert‐butyl‐4‐hydroxy‐5‐methylphenyl)propionyloxy]ethyl}‐2,4,8,10‐tetraoxaspiro[5,5]‐undecane (AO‐80) and their ternary systems were investigated. It was found that the dynamic mechanical properties of those systems depend on the colloidal properties, surface oxides, and surface modification of CB. For binary systems of CPE and CB, oxidized CB gives a high modulus at low strain amplitude and a large Payne effect compared with untreated CB. In contrast, the reverse effect was observed for their ternary systems. Consequently, a good micro‐dispersion is obtainable by surface modification due to physical adsorption of AO‐80 on oxidized CB particles via hydrogen bonds. © 2003 Society of Chemical Industry