Synthesis of novel chitosan–silica/CpG oligodeoxynucleotide nanohybrids with enhanced delivery efficiency

Chitosan–silica/CpG oligodeoxynucleotide (ODN) nanohybrids were synthesized to stimulate Toll-like receptor 9-mediated induction of interleukin-6 (IL-6). The chitosan–silica hybrid was first synthesized from a mixture of chitosan and 3-glycidoxypropyl trimethoxysilane under acidic conditions via a sol–gel process, and then used to condense CpG ODN2006x3-PD to yield chitosan–silica/CpG ODN nanohybrids. Scanning electron microscopy and atomic force microscopy showed that the chitosan–silica/CpG ODN nanohybrids had an elliptic shape with a diameter of 100–200 nm. After soaking in HAc–NaAc buffer solution (pH 5.5), the nanohybrids exhibited sustained release of CpG ODN. When the nanohybrids were separately exposed to 293XL-hTLR9 cells and peripheral blood mononuclear cells, no significant toxicity was observed. An immunochemical assay for cellular uptake revealed that the nanohybrids were taken up by the cells and located in endolysosomes. An enzyme-linked immunosorbent assay for cytokines indicated that the nanohybrids effectively stimulated the induction of IL-6. Chitosan–silica/CpG ODN nanohybrids underwent cellular uptake and enhanced induction of IL-6 to a greater degree than conventional chitosan/CpG ODN nanocomplexes, indicating that they have an enhanced delivery efficiency.     

Chemical Interrogation of the Malaria Kinome

Malaria, an infectious disease caused by eukaryotic parasites of the genus Plasmodium, afflicts hundreds of millions of people every year. Both the parasite and its host utilize protein kinases to regulate essential cellular processes. Bioinformatic analyses of parasite genomes predict at least 65 protein kinases, but their biological functions and therapeutic potential are largely unknown. We profiled 1358 small‐molecule kinase inhibitors to evaluate the role of both the human and the malaria kinomes in Plasmodium infection of liver cells, the parasites' obligatory but transient developmental stage that precedes the symptomatic blood stage. The screen identified several small molecules that inhibit parasite load in liver cells, some with nanomolar efficacy, and each compound was subsequently assessed for activity against blood‐stage malaria. Most of the screening hits inhibited both liver‐ and blood‐stage malaria parasites, which have dissimilar gene expression profiles and infect different host cells. Evaluation of existing kinase activity profiling data for the library members suggests that several kinases are essential to malaria parasites, including cyclin‐dependent kinases (CDKs), glycogen synthase kinases, and phosphoinositide‐3‐kinases. CDK inhibitors were found to bind to Plasmodium protein kinase 5, but it is likely that these compounds target multiple parasite kinases. The dual‐stage inhibition of the identified kinase inhibitors makes them useful chemical probes and promising starting points for antimalarial development.     

Magnetizing of permanent magnets using HTS bulk magnets

A demagnetized Nd–Fe–B permanent magnet was scanned just above the magnetic pole which contains the HTS bulk magnet generating a magnetic field of 3.27 T. The magnet sample was subsequently found to be fully magnetized in the open space of the static magnetic fields. We examined the magnetic field distributions when the magnetic poles were scanned twice to activate the magnet plate inversely with various overlap distances between the tracks of the bulk magnet. The magnetic field of the “rewritten” magnet reached the values of the magnetically saturated region of the material, showing steep gradients at the border of each magnetic pole. As a replacement for conventional pulse field magnetizing methods, this technique is proposed to expand the degree of freedom in the design of electromagnetic devices, and is proposed as a novel practical method for magnetizing rare-earth magnets, which have excellent magnetic performance and require intense fields of more than 3 T to be activated.     

Low‐order H∞ controller design on the frequency domain by partial optimization

In this paper, an optimization method of low‐order multivariable controllers for H_∞ control is proposed. Starting from a low‐order stabilizing controller, our method gives a sequence of controllers for which the H_∞ norm performance index is monotonically non‐increasing by tuning the numerator coefficient matrices of the low‐order controller. This controller class includes multivariable PID controllers. The proposed method is a descent method where the feasible direction is calculated by solving a linear matrix inequality that represents a sufficient condition for the H_∞ criterion for each frequency. Usefulness is shown by two numerical examples. Copyright © 2009 John Wiley & Sons, Ltd.     

High-gain and high-efficiency single-layer slotted waveguide arrayfor use in 22 GHz band

A slotted waveguide planar array using a single-layer feed circuit is proposed for high-frequency and high-gain antennas. The high efficiency of 75.6% and the gain of 35.9 dBi are obtained in the 22 GHz band, which confirms the potential of this type of antenna. The antenna consists of only two components, a slotted plate and a groove feed structure, and can be mass produced     

Kinesin family in murine central nervous system

In neuronal axons, various kinds of membranous components are transported along microtubules bidirectionally. However, only two kinds of mechanochemical motor proteins, kinesin and brain dynein, had been identified as transporters of membranous organelles in mammalian neurons. Recently, a series of genes that encode proteins closely related to kinesin heavy chain were identified in several organisms including Schizosaccharomyces pombe, Aspergillus niddulans, Saccharomyces cerevisiae, Caenorhabditus elegans, and Drosophila. Most of these members of the kinesin family are implicated in mechanisms of mitosis or meiosis. To address the mechanism of intracellular organelle transport at a molecular level, we have cloned and characterized five different members (KIF1-5), that encode the microtubule-associated motor domain homologous to kinesin heavy chain, in murine brain tissue. Homology analysis of amino acid sequence indicated that KIF1 and KIF5 are murine counterparts of unc104 and kinesin heavy chain, respectively, while KIF2, KIF3, and KIF4 are as yet unidentified new species. Complete amino acid sequence of KIF3 revealed that KIF3 consists of NH2-terminal motor domain, central alpha-helical rod domain, and COOH-terminal globular domain. Complete amino acid sequence of KIF2 revealed that KIF2 consists of NH2-terminal globular domain, central motor domain, and COOH-terminal alpha-helical rod domain. This is the first identification of the kinesin-related protein which has its motor domain at the central part in its primary structure. Northern blot analysis revealed that KIF1, KIF3, and KIF5 are expressed almost exclusively in murine brain, whereas KIF2 and KIF4 are expressed in brain as well as in other tissues. All these members of the kinesin family are expressed in the same type of neurons, and thus each one of them may transport its specific organelle in the murine central nervous system.     

Collagenous crystalloids in a fine needle aspirate of a pleomorphic adenoma of the minor salivary gland. A case report

BACKGROUND: Collagenous crystalloids were previously observed in histologic sections of pleomorphic adenoma. However, to the best of our knowledge, there have been no English-language reports dealing with collagenous crystalloids in fine needle aspirates. CASE: A fine needle aspiration specimen obtained from a mass in the hard palate of a 52-year-old female revealed collagenous crystalloids. The crystalloids were yellow to green, measured 30-50 microns in diameter and were radially arranged. CONCLUSION: This case indicates that collagenous crystalloids in salivary gland aspirates may be a clue to the diagnosis of pleomorphic adenoma.     

Effect of anti-macrophage migration inhibitory factor antibody on lipopolysaccharide-induced pulmonary neutrophil accumulation

Macrophage migration inhibitory factor (MIF) is a recently rediscovered pro-inflammatory cytokine that has the unique potential to override the anti-inflammatory action of glucocorticoids. Since recent reports suggest the pivotal role of MIF in acute lung injury, we examined the protective effect of anti-MIF antibody on lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were injected with LPS (7 mg/kg) intraperitoneally with or without pretreatment with anti-MIF antibody. The anti-MIF antibody significantly attenuated LPS-induced migration of neutrophils to the lungs at 4 and 24 h as demonstrated by observation of the number of neutrophils per alveolus, the activity of myeloperoxidase of the lung tissue, and cell differentiation of neutrophils in bronchoalveolar lavage (BAL) fluid. The increased level of macrophage inflammatory protein-2, a powerful neutrophil chemokine, in BAL fluid was also significantly attenuated by pretreatment with the anti-MIF antibody as compared with the control group. Additionally, positive immunostaining for MIF was observed in bronchial epithelial cells and alveolar macrophages, and Northern blot analysis of lung tissues demonstrated increased MIF mRNA 24 h after LPS injection. These data suggest that the anti-MIF antibody has therapeutic potential for the treatment of acute lung injury by suppressing the level of neutrophil chemokine in the lungs.     

Real-Time Orientation-Sensitive Magnetooptic Imager for Leakage Flux Inspection

We propose a new system for magnetooptical imaging that can observe the distributions of the amplitude and phase of an ac leakage magnetic field on a steel sheet driven externally by a dipole or a quadrature (rotating dipole) magnet. The new system, which we call a three-phase correlation image sensor (3PCIS), can perform two-dimensional imaging and parallel lock-in detection of the intensity-modulated light generated by a magnetooptic film and polarimetric techniques. We apply the imaging system to the leakage flux inspection of surface or near-surface defects of steel sheets and to the grain observation of electromagnetic steels. The imaging system allows us to observe the amplitude and phase (polarity for dipole excitation and defect orientation for quadrature excitation) of vertical flux components. The imager is also applicable to nonlinearity visualization via the harmonic responses of driving frequency, and provides rich clues for the horizontal flux components through observation of fine movements of domain walls of the magnetooptic film