Smart polyion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotides containing acid-labile linkages

A novel pH-sensitive and targetable antisense ODN delivery system based on multimolecular assembly into polyion complex (PIC) micelles of poly(L-lysine) (PLL) and a lactosylated poly(ethylene glycol)-antisense ODN conjugate (Lac-PEG-ODN) containing an acid-labile linkage (beta-propionate) between the PEG and ODN segments has been developed. The PIC micelles thus prepared had clustered lactose moieties on their peripheries and achieved a significant antisense effect against luciferase gene expression in HuH-7 cells (hepatoma cells), far more efficiently than that produced by the nonmicelle systems (ODN and Lac-PEG-ODN) alone, as well as by the lactose-free PIC micelle. In line with this pronounced antisense effect, the lactosylated PIC micelles showed better uptake than the lactose-free PIC micelles into HuH-7 cells; this suggested the involvement of an asialoglycoprotein (ASGP) receptor-mediated endocytosis process. Furthermore, a significant decrease in the antisense effect (27 % inhibition) was observed for a lactosylated PIC micelle without an acid-labile linkage (thiomaleimide linkage); this suggested the release of the active (free) antisense ODN molecules into the cellular interior in response to the pH decrease in the endosomal compartment is a key process in the antisense effect. Use of branched poly(ethylenimine) (B-PEI) instead of the PLL for PIC micellization led to a substantial decrease in the antisense effect, probably due to the buffer effect of the B-PEI in the endosome compartment, preventing the cleavage of the acid-labile linkage in the conjugate. The approach reported here is expected to be useful for the construction of smart intracellular delivery systems for antisense ODNs with therapeutic value.     

A theory of thin lamellar eutectic growth with anisotropic interphase boundaries

We present a semiempirical theory of the effects of an orientation dependence of the surface free energy of interphase boundaries (interphase boundary anisotropy) on lamellar eutectic growth in thin samples. We show that, to a good approximation, thin lamellar eutectic patterns with a strong interphase boundary anisotropy travel along the growth front at such a velocity – or, equivalently, at such an inclination angle of the lamellae left behind in the solid – that the surface tension force of the interphase boundary is nearly parallel to the applied thermal gradient. This explains, among other things, the crystallographic locking of lamellar eutectic patterns that occurs in those eutectic grains, which have cusp singularities in the Wulff plot of the interphase boundary. Based on this theory, we show that the rotating directional solidification method, by which a thin sample is rotated with respect to a fixed unidirectional thermal gradient, must yield eutectic lamellae whose trajectories are nearly homothetic to the two-dimensional Wulff form of the interphase boundary. This opens up new possibilities for the experimental study of interphase boundary anisotropy in eutectic alloys.     

The activation of furfuryl alcohol polymerization by oxygen and its enhanced mechanical properties

The effect of oxygen and additional oxygen providers on furfuryl alcohol polymerization was investigated through chemical analyses and mechanical evaluation. NMR, UV–vis, Fourier transform infrared, and gas chromatography–mass spectrometry (GC–MS) results suggested that atmospheric oxygen and the further addition of an oxygen source functioned as an activator for the entire network polymerization. Interestingly, the construction of a conjugated structure on the furan linear chain, which is key to three-dimensional cross-linking, also appears to be accelerated in the presence of oxygen. Furthermore, the introduction of oxygen providers into the curing system successfully enhanced the mechanical properties of the cured furan resin.     

Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.     

Administration of docosahexaenoic acid influences behavior and plasma catecholamine levels at times of psychological stress

The purpose of the present research was to clarify the effect of docosahexaenoic acid (DHA) intake on behavior and plasma catecholamines (CA). In Study 1, 42 students took either DHA-rich oil capsules containing 1.5–1.8 g DHA/d or control oil capsules containing 97% soybean oil plus 3% of another fish oil for 3 mon in a double-blind fashion. They took a psychological test (PF Study) at the start and end of the study. This study started at the end of summer vacation and ended just before the final exams. In the control group, external aggression (aggression against others) in PF Study was significantly increased at the end of the study as compared with that measured at the start (+8.9%), whereas it was not significantly changed in the DHA group (?1.0%). In a similar double-blind study (Study 2), we measured external aggression under nonstressful conditions. External aggression slightly decreased in the control group, whereas there were no significant changes in the DHA group. In Study 3 with 14 students, plasma CA were measured at the start and end of capsule administration period of 2 mon. Subjects were under continuous stress of the final exams that lasted throughout the whole study period. The ratio of plasma epinephrine to norepinephrine concentrations was significantly increased in the DHA group (78%), whereas it stayed at the same level in the control group. In Study 4, mice were fed either DHA-deficient diet or -sufficient diet for 4 wk, and their rearing frequency (an anxiety index) was measured. In the DHA-sufficient group, the rearing frequency was significantly less than in the other group. These effects of DHA intake may be applied to people in an attempt to ameliorate stress-related diseases.     

Physicochemical factors for discriminating between soluble and membrane proteins: hydrophobicity of helical segments and protein length

The average hydrophobicity of a polypeptide segment is consideredto be the most important factor in the formation of transmembranehelices, and the partitioning of the most hydrophobic (MH) segmentinto the alternative nonpolar environment, a membrane or hydrophobiccore of a globular protein may determine the type of proteinproduced. In order to elucidate the importance of the MH segmentin determining which of the two types of protein results froma given amino acid sequence, we statistically studied the characteristicsof MH helices, longer than 19 residues in length, in 97 membraneproteins whose three-dimensional structure or topology is known,as well as 397 soluble proteins selected from the Protein DataBank. The average hydrophobicity of MH helices in membrane proteinshad a characteristic relationship with the length of the protein.All MH helices in membrane proteins that were longer than 500residues had a hydrophobicity greater than 1.75 (Kyte and Doolittlescale), while the MH helices in membrane proteins smaller than100 residues could be as hydrophilic as 0.1. The possibilityof developing a method to discriminate membrane proteins fromsoluble ones, based on the effect of size on the type of proteinproduced, is discussed.     

Arithmetic Meyer sets and finite automata

Non-standard number representation has proved to be useful in the speed-up of some algorithms, and in the modelization of solids called quasicrystals. Using tools from automata theory we study the set of β-integers, that is, the set of real numbers which have a zero fractional part when expanded in a real base β, for a given β > 1. In particular, when β is a Pisot number — like the golden mean —, the set is a Meyer set, which implies that there exists a finite set F (which depends only on β) such that . Such a finite set F, even of minimal size, is not uniquely determined.In this paper we give a method to construct the sets F and an algorithm, whose complexity is exponential in time and space, to minimize their size. We also give a finite transducer that performs the decomposition of the elements of as a sum belonging to .     

Measurement method using coupled transmission lines for voltage transients on the distribution line

It is well known that voltage transients are caused by the operation of switchgears in a power system. The voltage transients travel along the power line as a traveling wave, and cause malfunction of electrical devices, communication systems, and the operational error of a control system. The voltage transients at the making operation of switchgear were examined to obtain the fundamental data for considering the immunity of communication systems used on a power system. However, it was difficult to observe the voltage transients using the potential transformer and the capacitance potential device because the transients were very rapid. Therefore, a measurement method using the coupled transmission line system is proposed to measure the high-speed and high-voltage transients, and the actual experimental results on the 6.9-kV power system are presented. This method enables the measurement of high-speed voltage transients in out of contact with the power system.     

Composite of Au nanoparticles and molecularly imprinted polymer as a sensing material

A molecularly imprinted polymer with immobilized Au nanoparticles (Au-MIP) is reported as a novel type of sensing material. The sensing mechanism is based upon the variable proximity of the Au nanoparticles immobilized in the imprinted polymer, which exhibits selective binding of a given analyte accompanied by swelling that causes a blue-shift in the plasmon absorption band of the immobilized Au nanoparticles. Using adrenaline as the model analyte, it was shown that molecular imprinting effectively enhanced the sensitivity and selectivity, and accordingly, Au-MIP selectively detects the analyte at 5 microM. The combination of molecular imprinting and the Au nanoparticle-based sensing system was shown to be a general strategy for constructing sensing materials in a tailor-made fashion due to wide applicability of the imprinting technique and the independence of the sensing mechanism from the analyte recognition system.     

Electrochemical Fabrication of Metallic Nanowires and Metal Oxide Nanopores

A nuclear track etched polycarbonate membrane filter with numerous cylindrical nanopores was applied as a nanoporous template for growing metallic nanowires. Nickel, cobalt, and iron nanowires were electrodeposited into the cylindrical nanopores. Cathodic polarization curves were measured to determine an optimum condition for growing nanowires. The shape of nanowires was observed using scanning electron microscope (SEM) and the crystal structure was analyzed using transmission electron microscopy (TEM). Diameter and length of nanowires corresponded to those of nanopores and each nanowire was composed of a single crystal. Anodized aluminum oxide films were also fabricated as a novel nanoporous template. The pore length and diameter was controlled changing anodizing conditions. Ordering behavior of nanopores array in an anodized aluminum oxide film was also investigated to make a novel nanoporous template with a highly ordered honeycomb array of nanopores.