Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

Synthesis of Metastable Tetragonal (t') Zirconia–Ceria Solid Solutions by the Polymerized Complex Method

Homogeneous metastable tetragonal ( t ') solid solutions of ZrO₂— x mol% CeO₂ ( x = 20 and 50) were successfully synthesized by the organic polymerized complex method. The citric acid-ethylene glycol solution containing Zr and Ce ions was polymerized at about 140°C and then heat-treated at about 350°C to obtain a precursor. The black precursor was heated at 450°C and then fired up to 1300° or 1590°C, resulting in the homogeneous solid solutions.     

Single-crystal growth and characterization of Cu2O and CuO

We have prepared a large number of crystals of cuprous oxide (Cu2O) by various procedures. Photoluminescence spectra of these crystals were studied to examine the concentration of defects, especially copper vacancy VCu to seek favourable conditions for growing Cu2O crystal. High-quality single crystals of Cu2O were prepared by the floating-zone melting method in air. Several synthetic crystals (specimens FA, FZ and GZ) and also a natural crystal were studied by X-ray analysis, inductively coupled plasma spectroscopy analysis, optical absorption, photoluminescence, photoconductivity and cyclotron resonance absorption, photoluminescence, photoconductivity and cyclotron resonance absorption to characterize their optical and electrical qualities. The best values of mobility and scattering time of photocarriers at T = 4.2 K are estimated to be h1.8 × 105 cm2 V–1 s–1 and h60 ps for positive holes, and 1.3 × 105 cm2 V–1 s–1 and 70 ps for electrons in Cu2O. Further, we report preliminary experimental results on transport property of crystals also of cupric oxide (CuO) purified by the floating-zone melting method.     

Lyapunov function-based obstacle avoidance scheme for a two-wheeled mobile robot

An obstacle avoidance scheme of a two-wheeled mobile robot is shown by selecting an appropriate Lya- punov function. When considering the obstacle, the Lyapunov function may have some local minima. A method which erases the local minima is proposed by using a function which covers the minima with a plane surface. The effectiveness of the proposed method is verified by numerical simulations.     

An application of the 2-nitrobenzenesulfenyl method to proteomic profiling of human colorectal carcinoma: A novel approach for biomarker discovery

In the development of novel biomarkers, the proteomic approach is advantageous because using it the cancer-associated proteins can be directly identified. We previously developed a 2-nitrobenzenesulfenyl (NBS) method to improve quantitative proteome analysis. Here, we applied this method to proteomic profiling of colorectal carcinoma (CRC) to identify novel proteins with altered expression in CRC. Each pair of tumor and normal tissue specimens from 12 CRC patients was analyzed, and approximately 5000 NBS-labeled paired peaks were quantified. Peaks with altered signal intensities (>1.5-fold) and occurring frequently in the samples (>70%) were selected, and 128 proteins were identified by MS/MS analyses as differentially expressed proteins in CRC tissues. Many proteins were newly revealed to be CRC related; 30 were reported in earlier studies of CRC. Six proteins that were up-regulated in CRC (ZYX, RAN, RCN1, AHCY, LGALS1, and VIM) were further characterized and validated by Western blot and immunohistochemistry. All six were found to be CRC-localized, either in cancer cells or in stroma cells near the cancer cells. These results indicate that the proteins identified in this study are novel candidates for CRC markers, and that the NBS method is useful in proteome mining to discover novel biomarkers.     

Advanced coded-aperture imaging system for nuclear medicine

An advanced coded imaging system is described, and some results of phantom experiments are presented. The advanced method uses a pair of coherent codes (+ 1 and -1 codes) and has many advantages compared with conventional ones. One of the greatest advantages is that there are no sidelobes in the focal plane and only a few in other planes. Therefore, when an object can be regarded as two-dimensional, it is perfectly reconstructed with high detecting efficiency, and this is successfully simulated by a thyroid phantom with 99mTc. Moreover, this system has an ability to reconstruct tomograms, which is also shown by using ring phantoms piled on one another with some cold spots in their shells. From these experimental results it may be concluded that the new system is useful for practical applications, for example, to nuclear medicine.     

Route guidance by a car navigation system based on augmented reality

Car navigation systems play a prominent role in road traffic safety and traffic regulation. However, it is necessary to improve the route guidance of car navigation systems so that they accurately and quickly recognize small differences in location. Thus, to increase the ease of understanding and safety of car navigation systems, navigation systems based on augmented reality have been proposed for providing guidance at road intersections. We are currently developing a car navigation system based on augmented reality, called AR‐Navi. We investigated designs for the display of road intersection guidance that can be easily understood even when limited information is available and proposed a “best shot” display method that does not use moving images. In addition, we implemented a prototype system that includes these methods and conducted driving experiments on public roads to evaluate the ease of understanding and safety of AR‐Navi. Using the evaluation results, we confirmed that the ease of understanding and safety is similar in the case of AR‐Navi and CG‐Navi. We also clarified the characteristics of AR‐Navi. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 180(2): 43–54, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.22278     

One-step route to a hybrid TiO2/TixW1?xN nanocomposite by in situ selective carbothermal nitridation

Metal oxide/nitride nanocomposites have many existing and potential applications, e.g. in energy conversion or ammonia synthesis. Here, a hybrid oxide/nitride nanocomposite (anatase/Ti_xW_1−xN) was synthesized by an ammonia-free sol–gel route. Synchrotron x-ray diffraction, complemented with electron microscopy and thermogravimetric analysis, was used to study the structure, composition and mechanism of formation of the nanocomposite. The nanocomposite contained nanoparticles (<5 nm diameter) of two highly intermixed phases. This was found to arise from controlled nucleation and growth of a single oxide intermediate from the gel precursor, followed by phase separation and in situ selective carbothermal nitridation. Depending on the preparation conditions, the composition varied from anatase/Ti_xW_1−xN at low W content to an isostructural mixture of Ti-rich and W-rich Ti_xW_1−xN at high W content. In situ selective carbothermal nitridation offers a facile route to the synthesis of nitride-oxide nanocomposites. This conceptually new approach is a significant advance from previous methods, which generally require ammonolysis of a pre-synthesized oxide.     

Brain Mechanisms of Exercise-Induced Hypoalgesia: To Find a Way Out from “Fear-Avoidance Belief”

It is well known that exercise produces analgesic effects (exercise-induced hypoalgesia (EIH)) in animal models and chronic pain patients, but the brain mechanisms underlying these EIH effects, especially concerning the emotional aspects of pain, are not yet fully understood. In this review, we describe drastic changes in the mesocorticolimbic system of the brain which permit the induction of EIH effects. The amygdala (Amyg) is a critical node for the regulation of emotions, such as fear and anxiety, which are closely associated with chronic pain. In our recent studies using neuropathic pain (NPP) model mice, we extensively examined the association between the Amyg and EIH effects. We found that voluntary exercise (VE) activated glutamate (Glu) neurons in the medial basal Amyg projecting to the nucleus accumbens (NAc) lateral shell, while it almost completely suppressed NPP-induced activation of GABA neurons in the central nucleus of the Amyg (CeA). Furthermore, VE significantly inhibited activation of pyramidal neurons in the ventral hippocampus-CA1 region, which play important roles in contextual fear conditioning and the retrieval of fear memory. This review describes novel information concerning the brain mechanisms underlying EIH effects as a result of overcoming the fear-avoidance belief of chronic pain.     

Interactive segmentation of the cerebral lobes with fuzzy inference in 3T MR images.

Measurement of volume and surface area of the frontal, parietal, temporal and occipital lobes from magnetic resonance (MR) images shows promise as a method for use in diagnosis of dementia. This article presents a novel computer-aided system for automatically segmenting the cerebral lobes from 3T human brain MR images. Until now, the anatomical definition of cerebral lobes on the cerebral cortex is somewhat vague for use in automatic delineation of boundary lines, and there is no definition of cerebral lobes in the interior of the cerebrum. Therefore, we have developed a new method for defining cerebral lobes on the cerebral cortex and in the interior of the cerebrum. The proposed method determines the boundaries between the lobes by deforming initial surfaces. The initial surfaces are automatically determined based on user-given landmarks. They are smoothed and deformed so that the deforming boundaries run along the hourglass portion of the three-dimensional shape of the cerebrum with fuzzy rule-based active contour and surface models. The cerebrum is divided into the cerebral lobes according to the boundaries determined using this method. The reproducibility of our system with a given subject was assessed by examining the variability of volume and surface area in three healthy subjects, with measurements performed by three beginners and one expert user. The experimental results show that our system segments the cerebral lobes with high reproducibility.