Development of Novel Inhibitors for Histone Methyltransferase SET7/9 based on Cyproheptadine

The histone methyltransferase SET7/9 methylates not only histone but also non‐histone proteins as substrates, and therefore, SET7/9 inhibitors are considered candidates for the treatment of diseases. Previously, our group identified cyproheptadine, used clinically as a serotonin receptor antagonist and histamine receptor (H1) antagonist, as a novel scaffold of the SET7/9 inhibitor. In this work, we focused on dibenzosuberene as a substructure of cyproheptadine and synthesized derivatives with various functional groups. Among them, the compound bearing a 2‐hydroxy group showed the most potent activity. On the other hand, a 3‐hydroxy group or another hydrophilic functional group such as acetamide decreased the activity. Structural analysis clarified a rationale for the improved potency only by tightly restricted location and type of the hydrophilic group. In addition, a SET7/9 loop, which was only partially visible in the complex with cyproheptadine, became more clearly visible in the complex with 2‐hydroxycyproheptadine. These results are expected to be helpful for further structure‐based development of SET7/9 inhibitors.     

Chain stiffness and chain conformation of poly(α-methylene-γ-butyrolactone) in dilute solutions

The chain stiffness and local chain conformation of atactic poly(α-methylene-γ-butyrolactone) (PMBL), which is a side chain cyclic structural analog of poly(methyl methacrylate) (PMMA), with a weight-average molecular weight (M_w) ranging from 2.8 × 10³ to 2.6 × 10⁶ in N,N-dimethylformamide (DMF) and γ-butyrolactone (GBL) were characterized by size exclusion chromatography with a multi-angle light-scattering detector (SEC-MALS) and synchrotron radiation small-angle X-ray scattering (SAXS). Based on the Kratky-Porod worm-like chain model, the scattering functions and the M_w dependence of z-average root-mean-square radius of gyration <S²>_z^1/2 yielded the Kuhn segment lengths λ⁻¹, the diameter of the PMBL chains d, and the excluded-volume strengths in DMF and GBL. The local conformation of atactic PMBL in DMF and GBL were slightly larger than those of atactic PMMA, due to the presence of the conformationally rigid lactone ring structure.     

Te concentration dependent photoemission and inverse-photoemission study of FeSe1?xTex

We have characterized the electronic structure of FeSe_1−xTe_x for various x values using soft x-ray photoemission spectroscopy (SXPES), high-resolution photoemission spectroscopy (HRPES) and inverse photoemission spectroscopy (IPES). The SXPES valence band spectral shape shows that the 2 eV feature in FeSe, which was ascribed to the lower Hubbard band in previous theoretical studies, becomes less prominent with increasing x. HRPES exhibits systematic x dependence of the structure near the Fermi level (E_F): its splitting near E_F and filling of the pseudogap in FeSe. IPES shows two features, near E_F and approximately 6 eV above E_F; the former may be related to the Fe 3d states hybridized with chalcogenide p states, while the latter may consist of plane-wave-like and Se d components. In the incident electron energy dependence of IPES, the density of states near E_F for FeSe and FeTe has the Fano lineshape characteristic of resonant behavior. These compounds exhibit different resonance profiles, which may reflect the differences in their electronic structures. By combining the PES and IPES data the on-site Coulomb energy was estimated at 3.5 eV for FeSe.     

Locomotion Control of MEMS Microrobot Using Pulse‐Type Hardware Neural Networks

This paper presents the locomotion control of a microelectromechanical system (MEMS) microrobot. The MEMS microrobot demonstrates locomotion control by pulse‐type hardware neural networks (P‐HNN). P‐HNN generate oscillatory patterns of electrical activity like those of living organisms. The basic component of P‐HNN is a pulse‐type hardware neuron model (P‐HNM). The P‐HNM has the same basic features as biological neurons, such as the threshold, the refractory period, and spatiotemporal summation characteristics, and allows the generation of continuous action potentials. P‐HNN has been constructed with MOSFETs and can be integrated by CMOS technology. Like living organisms, P‐HNN has realized robot control without using software programs or A/D converters. The size of the microrobot fabricated by MEMS technology was 4 × 4 × 3.5 mm. The frame of the robot was made of a silicon wafer, equipped with rotary actuators, link mechanisms, and six legs. The MEMS microrobot emulated the locomotion method and the neural networks of an insect by rotary actuators, link mechanisms, and the P‐HNN. We show that the P‐HNN can control the forward and backward locomotion of the fabricated MEMS microrobot, and that it is possible to switch its direction by inputting an external trigger pulse. The locomotion speed was 19.5 mm/min and the step size was 1.3 mm. © 2013 Wiley Periodicals, Inc. Electr Eng Jpn, 186(3): 43–50, 2014; Published online in Wiley Online Library ( wileyonlinelibrary.com ). DOI 10.1002/eej.22473     

Efficient synthesis and magnetic properties of triphenylamine bearing three nitronylnitroxide radicals

Improved synthesis and reinvestigation of the magnetic properties of triphenylamine bearing three nitronylnitroxide radicals (1) were carried out. Single crystal X-ray crystallographic analysis of 1 established that its molecular shape had a C₃-symmetry. Our newly prepared 1 showed different physical properties from those of reported. SQUID measurements of 1 showed that each of the three spins of 1 behaved independently at room temperature. In contrast, the three spins coupled antiferromagnetically at lower temperature as low as ca. 1.8 K. These spin behaviors can be explained by a regular triangular antiferromagnetic model (J/k_B = ?3.3 K) and interpreted as a spin frustration system.     

Modulation of nanotube formation in apatite single crystal via organic molecule incorporation

Hydroxyapatite materials are potentially useful for biomedical application, especially as vehicles for functional molecules. Structural control of bulk apatite materials, such as in the fabrication of hollow microspheres or porous structures, has been studied for this purpose. However, control of the internal structure of the source apatite crystal itself is still a challenge. Here, we show that small organic molecules incorporated in apatite crystals act as porogens which control the porous structure of apatite single crystal. The presence of amino acid under apatite synthesis conditions leads to firm bindings and encapsulation of the amino acid in apatite single crystals. Amino acid elimination by heating or electron beam irradiation enhances the pore formation in apatite single crystal. Moreover, incorporation of an acidic amino acid in apatite induces peapod like nanotubes in apatite single crystals. This study suggests the potential of using small organics for nano-structural control of apatite single crystals which would be valuable for enhancing drug loadings or modulating material digestion in vivo.     

Decomposition characteristics of biodegradable plastics made from sago starch‐extraction residue

Biodegradable plastics were synthesized for the effective use of sago starch‐extraction residue, which has been discarded as a waste. Two types of esterified sago starch‐extraction residue, P‐SP and L‐SP, were obtained. It had black color for P‐SP₁₆₀ (esterified by palm oil) to light yellow color for L‐SP₈₀ (esterified by lauric acid) and showed high carbon content, ranging from 399.3 to 537.1 g kg⁻¹. Biodegradable plastics from the residue, which had high esterification degree showed thermoplasticity and slower decomposition in Andisols in Japan and Inceptisols in Philippines. The esterification degrees of P‐SP₁₆₀ and L‐SP were 3.23 and 2.95 to 5.18 mmol g⁻¹, respectively. In addition, L‐SP₈₀ exhibited the most appropriate thermal softening behavior by heating. The cumulative decomposition of P‐SP₁₆₀ in Andisols and Inceptisols showed 16.7 and 32.8% of total carbon during 31 day of the incubation. On the other hand, the decomposition rates of L‐SP₈₀ in Andisols and Inceptisols were less than 10% of total carbon during 31 day of the incubation. The addition of triacetin as plasticizer to P‐SP₁₆₀ and L‐SP₈₀ remarkably influenced the decomposition rate of both molded P‐SP₁₆₀ and L‐SP₈₀. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Evaluation of high‐temperature ductility in weld metal. Study of reheat cracking in metal active‐gas welding with flux‐cored wire stainless steel weld metal (2nd Report)

The special features of the weldability of high-strength low-carbon microalloyed steels are investigated.     

Aroma Characteristic and Volatile Profiling of Carrot Varieties and Quantitative Role of Terpenoid Compounds for Carrot Sensory Attributes

The aroma characteristics and volatile profiles of 14 carrot varieties were investigated by sensory evaluations and gas chromatography–mass spectrometry volatile analyses. The sensory map obtained by principal components analysis showed that the sensory attributes comprised 3 categories: sour/green, overall carrot/harsh/ink‐like, and fruity/fresh/sweet. The Kuroda type is characterized by lower intensities of overall carrot/harsh/ink‐like and fruity/fresh/sweet notes. Furthermore, volatile profiling indicated that this type did not have significantly higher amounts of volatiles. Partial least squares regression analysis determined the quantitative contributions to ink‐like, harsh, and fruity carrot aromas; monoterpenes had significant positive correlations with these attributes, while bisabolene isomers had negative correlations. The aroma attribute intensity and contents of volatiles and nutritional compounds are relatively low in the Kuroda type than in other carrot types. This type may be useful for reducing carrot harshness during the development of new carrots with good eating qualities.     

Adenovirally expressed basic fibroblast growth factor rescues photoreceptor cells in RCS rats

OBJECTIVE: To examine the efficacy of an antileukocyte adhesion antibody (anti-CD18) as an adjuvant for delayed (2 hours and 4 hours) thrombolytic therapy (recombinant human tissue plasminogen activator [rt-PA]) in middle cerebral artery occlusion (MCAO) in rats. BACKGROUND: Thrombolytic therapy with rt-PA is limited in its application by a short therapeutic window. METHODS: Male Wistar rats were subjected to MCAO by a single fibrin-rich clot. The rats were assigned to the following experimental groups: Experiment 1 (treatment 2 hours after embolization), 1) rt-PA, 2) anti-CD18 antibody, 3) rt-PA and anti-CD18 antibody, 4) immunoglobulin (Ig) G, and 5) vehicle; Experiment 2 (treatment 4 hours after occlusion), 1) rt-PA alone, 2) rt-PA and anti-CD18 antibody, and 3) nontreated control group. Neurologic deficits, infarction volume, hemorrhage, and brain myeloperoxidase (MPO) immunoreactivity were measured. Results: Administration of rt-PA and anti-CD18 antibody 2 hours later reduced significantly (p < 0.05) the infarct volume and improved neurologic deficits compared with the vehicle-treated group. Treatment with rt-PA alone improved neurologic deficits significantly and reduced mean infarct volume compared with the vehicle-treated group. However, treatment with anti-CD18 antibody neither reduced infarct volume nor improved neurologic deficits compared with the IgG-treated group. The combination of rt-PA and anti-CD18 antibody treatment at 4 hours reduced significantly the infarct volume and MPO immunoreactive cells compared with rt-PA treatment alone at 4 hours, and reduced neurologic deficits compared with rt-PA treatment alone and compared with the nontreated animals. CONCLUSIONS: The combination of antileukocyte adhesion antibody and thrombolytic therapy may increase the therapeutic window for the treatment of stroke.